ANTI-INFECTIVE PYRIMIDINES NND USES THEREOF CROSS-REFERENCE TO RELNTED PNTENT NPPLICNTIONS [0001] This patent application claims priority to U S Provisional Patent Npplication No 60972,881 (filed September 17, 2007) and U S Provisional Patent Npplication No 61096,792 (filed September 13, 2008) The entire text of those applications is incorporated by reference into this application FIELD OF THE FNVENTION [0002] This invention is directed to (a) compounds and sahs thereof that, inter aha, are useful as hepatitis C virus (HCV) inhibitors, (b) intermediates useful for the preparation of such compounds and salts, (c) compositions comprising such compounds and salts, (d) methods for preparmg such intermediates, compounds, salts, and compositions, (e) methods of use of such compounds, salts, and compositions, and (f) kits comprising such compounds, salts, and compositions BNCKGROUND OF THE INVENTION [0003] Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called HCV Nt least six different HCV genotypes (with several subtypes within each genotype) are known to date In North Nmerica, HCV genotype la pred0mlnates, followed by HCV genotypes 1b, 2a, 2b, and 3a In the United States, HCV genotypes 1, 2, and 3 are the most common, with about 80% of the hepatitis C patients having HCV genotype 1 In Europe, HCV genotype 1b is pred0mlnant, followed by HCV genotypes 2a, 2b, 2c, and 3a HCV genotypes 4 and 5 are found almost exclusively in Nfrica Ns discussed below, the patients HCV genotype is clinically important in determining the patients potential response to therapy and the required duration of such therapy [0004] Nn HCV infection can cause liver inflammation (hepatitis) that is often asymptomatic, but ensuing chronic hepatitis can result in cirrhosis of the liver (fibrotic scarring of the liver), liver cancer, andor liver failure The World Health Organization estimates that about 170 million persons worldwide are chronically infected with HCV, and from about three to about four million persons are newly infected globally each year Nccording to the Centers for Disease Control and Prevention, about four million people in the United States are infected with HCV C0-mfection with the human immunodeficiency virus (HFV) IS common, and rates of HCV infection among HIV positive populations are higher [0005] There is a small chance of clearing the virus spontaneously, but the majority of patients with chronic hepatitis C will not clear it without treatment Indications for treatment typically include proven HCV infection and persistent abnormal liver function tests There are two treatment regimens that are primarily used to treat hepatitis C monotherapy (using an interferon agent - either a conventional or longer-acting pegylated interferon) and combination therapy (using an interferon agent and ribavirin) Interferon, which is injected into the bloodstream, works by bolstering the immune response to HCV, and ribavirin, which is taken orally, is believed to work by preventing HCV replication Taken alone, ribavirin does not effectively suppress HCV levels but an interferonribavirin combination is more effective than interferon alone Typically, hepatitis C is treated with a combination of pegylated interferon alpha and ribavirin for a period of 24 or 48 weeks, depending on the HCV genotype [0006] The goal of treatment is sustained viral response — meaning that HCV is not measurable m the blood after therapy is completed Following treatment with a combination of pegylated interferon alpha and ribavirin, sustained cure rates (sustained viral response) of about 75% or better occur in people with HCV genotypes 2 and 3 in 24 weeks of treatment, about 50% in those with HCV genotype 1 with 48 weeks of treatment, and about 65% in those with HCV genotype 4 in 48 weeks of treatment [0007] Treatment may be physically demanding, particularly for those with prior history of drug or alcohol abuse, because both interferon and ribavirin have numerous side effects Common interferon-associated side effects include flu-like symptoms, extreme fatigue, nausea, loss of appetite, thyroid problems, high blood sugar, hair loss, and skin reactions at the injection site Possible serious interferon-associated side effects include psychoses (e g, suicidal behavior), heart problems (e g, heart attack, low blood pressure), other internal organ damage, blood problems (e g, blood counts falling dangerously low), and new or worsening autoimmune disease (e g, rheumatoid arthritis) Ribavirm-associated side effects include anemia, fatigue, irritability, skin rash, nasal stuffiness, sinusitis, and cough Ribavirin can also cause birth defects, so pregnancy in female patients and female partners of male patients must be avoided during treatment and for six months afterward [0008] Some patients do not complete treatment because of the serious side effects discussed above, other patients (non-responders) continue to have measurable HCV levels despite treatment, and yet other patients (relapsers) clear the virus during therapy, but the virus returns sometime after completion of the treatment regimen Thus, there continues to be a need for alternative compounds, compositions, and methods of treatment (used either in combination with or in lieu of an interferon agent andor ribavirin) to alleviate the symptoms of hepatitis C, thereby providing partial or complete relief This invention provides compounds (including salts thereof), compositions, and methods of treatment that generally address such a need SUMMNRY OF THE INVENTION [0009] This invention is directed to compounds that correspond in structure to formula I-LO (Formula Removed) 010] In formula I-LO ---- is selected from the group consisting of smgle carbon-carbon bond and double carbon-carbon bond, R1 IS selected from the group consisting of hydr0gen, methyl, and nitr0gen-protecting group, R2 is selected from the group consisting of hydr0gen, halo, hydroxy, methyl, cyclopropyl, and cyclobutyl, R3 is selected from the group consisting of hydr0gen, halo, oxo, and methyl, R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, wherein (a) the ammo, aminocarbonyl, and aminosulfonyl optionally are substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, or (2) two substituents that, t0gether with the amino nitr0gen, form a single-ring heterocyclyl, and (b) the alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, and alkylsulfonyl, optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, ammo, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, t0gether with the amino nitr0gen, form a single-nng heterocyclyl, and (c) the carbocyclyl and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl halo, oxo, nitro, cyano, azido, hydroxy, amino alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, t0gether with the amino nitr0gen, form a single-ring heterocyclyl, R5 is selected from the group consisting of hydr0gen, hydroxy, alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, carbocyclylsulfonyloxy, haloalkylsulfonyloxy, and halo, R6 is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of RE, RF, RG, RH, RI, RJ, and RK, each RE is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, cyano, amino, imino, azido, and aldehydo, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, each RF is independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, azido, 0X0, ammosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the ammo, imino, ammosulfonyl, aminocarbonyl, carbocyclyl, and heterocyclyl optionally are substituted with one or two substituents mdependently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, alkylsulfonylamino, hydroxy, and alkyloxy, wherein amino portion of the alkylsulfonylamino optionally is substituted with a substituent selected from the group consisting of alkyl, alkenyl, and alkynyl. each RG is independently selected from the group consisting of carbocyclyl and heterocyclyl, wherein each such substituent optionall) is substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl each RH IS independently selected from the group consisting of alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, and alkynylsulfonyloxy, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the ammo, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl, each R1 IS independently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, aminocarbonyl, alkyloxycarbonyl, carbocyclylcarbonyl, and heterocyclylcarbonyl, wherein (a) the alkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxyalkyl, carbocyclyl, heterocyclyl, alkylsulfonyl, and alkylsulfonylamino, wherein the carbocyclyl and heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of halo, alkyl, and oxo, each RJ is independently selected from the group consisting of carbocyclylsulfonylammo, heterocyclylsulfonylammo, alkylcarbonylamino, alkenylcarbonylammo, alkynylcarbonylamino, alkyloxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylamino, alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, ammocarbonylamino, alkyloxycarbonylaminoimino, alkylsulfonylaminoimmo, alkenylsulfonylaminoimino, and alkynylsulfonylaminoimino, wherein (a) the ammo portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl alkylcarbony loxy, aminocarbonylalkyl, alkyl, alkenyl, alkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyi optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, halo, 0X0, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, and alkynyloxy, wherein the alkyl optionally is substituted with one or more hydroxy, (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, and ammo, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, and each R is independently selected from the group consisting of ammosulfonyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl, wherein (a) the alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl optionally are substituted with one or more substituents mdependently selected from the group consistmg of carboxy, hydroxy, halo amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbooyolyl, heterocyclyl, cvano, and aminocarbonyl, wherem the amino, ammosuifonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyi, and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected from the group consistmg of alkyl, alkenyl, and alkynyi [0011] This invention also is directed to the salts (including pharmaceutically acceptable salts) of the compounds of the invention [0012] This invention also is directed to compositions (including pharmaceutical compositions) that comprise one or more compounds andor salts of the invention, and, optionally, one or more additional therapeutic agents [0013] This invention also is directed to kits that comprise one or more compounds andor salts of the invention, and, optionally, one or more additional therapeutic agents [0014] This invention also is directed to methods of use of the compounds, salts, compositions, andor kits of the invention to, for example, inhibit replication of an RNN virus (including HCV), treat a disease treatable by inhibiting HCV ribonucleic acid (RNN) polymerase (including hepatitis C) [0015] This invention also is directed to a use of one or more compounds andor salts of the invention to prepare a medicament The medicament optionally can comprise one or more additional therapeutic agents In some embodiments, the medicament is useful for treating hepatitis C [0016] Further benefits of Npplicants invention will be apparent to one skilled in the art from reading this patent application BRIEF DESCRIPTION OF THE DRNWINGS [0017] Figure 1 shows an illustrative PXRD pattern for the ethanol solvate of compound IB-L0-2 3 [0018] Figure 2 shows an illustrative TGN profile of the ethanol solvate of compound IB-L0-2 3 [0019] Figure 3 shows an illustrative PXRD pattern for the acetonitrile solvate of compound IB-L0-2 3 [0020] Figure 4 shows an illustrative PXRD pattern for the ethyl acetate solvate of compound IB-L0-2 3 [0021] Figure 5 shows an illustrative PXRD pattern for the 2-propanol solvate of compound IB-L0-2.3 [0022] Figure 6 shows an illustrative PXRD pattern for the methanol solvate of compound IB-L0-2 3 10023] Figure 7 shows an illustrative PXRD pattern for the 1-propanol solvate of compound IB-L0-2.3 [0024] Figure 8 shows an illustrative PXRD pattern for the solvent free crystalline compound IB-L0-2 3 [0025] Figure 9 shows an illustrative PXRD pattern for the hydrate of compound IB-L0-2 3 [0026] Figure 10 shows an illustrative PXRD pattern for the pattern N monosodium sah of compound IB-L0-2 3. [0027] Figure 11 shows an illustrative TGN profile of the pattern N monosodium salt of compound IB-L0-2 3 [0028] Figure 12 shows an illustrative PXRD pattern for the pattern B monosodium salt of compound IB-L0-2 3 [0029] Figure 13 shows an illustrative TGN profile of the pattern B monosodium sah of compound IB-L0-2 3 [0030] Figure 14 shows an illustrative PXRD pattern for the pattern C monosodium salt of compound IB-L0-2 3, [0031] Figure 15 shows an illustrative PXRD pattern for the disodium salt of compound IB-L0-2 3 ]0032] Figure 16 shows an illustrative TGN profile of the disodium salt of compound IB-L0-2 3 [0033] Figure 17 shows an illustrative PXRD pattern for the monopotassium salt of compound IB-L0-2 3. [0034| Figure 18 shows an illustrative TGN profile of the monopotassium salt of compound IB-L0-2 3 [0035] Figure 19 shows an illustrative PXRD pattern for the pattern N monochohne salt of compound IB-L0-2 3 [0036] Figure 20 shows an illustrative TGN profile of the pattern N monochohne salt of compound IB-L0-2.3. 10037] Figure 21 shows an illustrative PXRD pattern for the pattern B monochohne salt of compound IB-L0-2 3 [0038] Figure 22 shows an illustrative TGN profile of the pattern B monochohne salt of compound IB-L0-2 3 [0039] Figure 23 shows an illustrative PXRD pattern for the dicholme salt of compound IB-L0-2 3 DETNILED DESCRIPTION OF THE INVENTION [0040] This detailed description is intended only to acquaint others skilled in the art with Npplicants invention, its principles, and its practical application so that others skilled in the art may adapt and apply the invention in its numerous forms, as they may be best suited to the requirements of a particular use This description and its specific examples are intended for purposes of illustration only This invention, therefore, is not limited to the embodiments descnbed m this patent application, and may be variously modified N Definitions [0041] The term alkyl (alone or in combination with another term(s)) means a straight-or branched-chain saturated hydrocarbyl substituent typically containing from 1 to about 20 carbon atoms, more typically from 1 to about 8 carbon atoms, and even more typically from 1 to about 6 carbon atoms Examples of such substituents include methyl, ethyl, n-prop>l, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, is0-amyl, and hexy! Ns m this definition, throughout this detailed description Npplicants have provided illustrative examples The provision of such illustrative examples should not be interpreted as if the provided illustrative examples are the only options available to one skilled in the art 10042] The term alkenyl (alone or in combination with another term(s)) means a straight- or branched-chain hydrocarbyl substituent containing one or more double bonds and typically fiom 2 to about 20 carbon atoms, more typically from about 2 to about 8 carbon atoms, and even more typically from about 2 to about 6 carbon atoms Examples of such substituents include ethenyl (vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl, 1,4-butadienyl, 1-butenyl, 2-butenyl, and 3-butenyl [0043] The term alkynyl (alone or in combination with another term(s)) means d straight- or branched-chain hydrocarbyl substituent containing one or more triple bonds and typically from 2 to about 20 carbon atoms, more typically from about 2 to about 8 carbon atoms, and even more typically from about 2 to about 6 carbon atoms Examples of such substituents include ethynyl, 2-propynyl, 3-propynyl, 2-butynyl, and 3-butynyl ]0044] The term carbocyclyl (alone or in combination with another term(s)) means a saturated cyclic (i e , cycloalkyi), partially saturated cyclic ( e , cycloalkenyl), or completely unsaturated ( e , aryl) hydrocarbyl substituent containing from 3 to 14 carbon ring atoms (ring atoms are the atoms bound t0gether to form the ring or rings of a cyclic substituent) N carbocyclyl may be a single ring, which typically contains from 3 to 6 ring atoms Examples of such single-nng carbocyciyls include cyclopropyl (cyclopropanyl), cyclobutyl (cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl, cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl, cyclohexadienyl, and phenyl N carbocyclyl alternatively may be 2 or 3 rings fused t0gether, such as naphthalenyl, tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl), anthracenyl, phenanthrenyl, and decalinyl 10045] The term cycloalkyi (alone or in combination with another term(s)) means a saturated cyclic hydrocarbyl substituent containing from 3 to 14 carbon ring atoms N cycloalkyi may be a single carbon ring, which typically contains from 3 to 6 carbon ring atoms Examples of single-ring cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl N cycloalkyi alternatively may be 2 or 3 carbon rings fused t0gether, such as, decalinyl [0046] The term aryl (alone or in combination with another term(s)) means an aromatic carbocyclyl containing from 6 to 14 carbon ring atoms Examples of aryls include phenyl, naphthalenyl, and indenyl [0047] In some instances, the number of carbon atoms in a hydrocarbyl substituent (e g , alkyl, alkenyl, alkynyl, or cycloalkyi) is indicated by the prefix Cx-Cy-, wherein x is the minimum and y is the maximum number of carbon atoms in the substituent Thus, for example, C1-C6-alkyl refers to an alkyl substituent containing from 1 to 6 carbon atoms Illustrating further, C3-C6-cycloalkyl means a saturated hydrocarbyl ring containing from 3 to 6 carbon ring atoms [0048] The term hydr0gen (alone or in combination with another tenn(s)) means a hydr0gen radical, and may be depicted as -H [0049] The term hydroxy (alone or in combination with another term(s)) means -OH [0050] The term nitro (alone or in combination with another term(s)) means -NO2 [0051] The term cyano (alone or in combination with another term(s)) means -CN which also may be depicted as -C≡N [0052] The term keto (alone or in combination with another term(s)) means an oxo radical, and may be depicted as =O [0053] The term carboxy (alone or in combination with another term(s)) means -C(O)-OH [0054] The term amino (alone or in combination with another term(s)) means -NH2 [0055] The term imino (alone or in combination with another term(s)) means =NH [0056] The term ammoimino (alone or in combination with another term(s)) means =NNH2 [0057] The term hal0gen or halo (alone or in combination with another term(s)) means a fluorine radical (which may be depicted as -F), chlorine radical (which may be depicted as -Cl), br0mlne radical (which may be depicted as -Br), or iodine radical (which may be depicted as -I) [0058] N substituent is substitutable if it comprises at least one carbon or nitr0gen atom that is bonded to one or more hydr0gen atoms Thus, for example, hydr0gen, hal0gen, and cyano do not fall within this definition In addition, a sulfur atom in a heterocyclyl containing such atom is substitutable with one or two oxo substituents [0059[ If a substituent is described as being substituted, a non-hydr0gen radical is in the place of hydr0gen radical on a carbon or nitr0gen of the substituent Thus, for example, a substituted alkyl substituent is an alkyl substituent in which at least one non-hydr0gen radical is in the place of a hydr0gen radical on the alkyl substituent To illustrate, monofluoroalkyl is alkyl substituted with a fluoro radical, and difluoroalkyl is alkyl substituted with two fluoro radicals It should be rec0gnized that if there are more than one substitution on a substituent, each non-hydr0gen radical may be identical or different (unless otherwise stated) [0060] If a substituent is described as being optionally substituted, the substituent may be either (1) not substituted or (2) substituted If a substituent is described as being optionally substituted with up to a particular number of non-hydr0gen radicals, that substituent may be either (1) not substituted, or (2) substituted by up to that particular number of non-hydr0gen radicals or by up to the maximum number of substitutable positions on the substituent, whichever is less Thus, for example, if a substituent is described as a heteroaryl optionally substituted with up to 3 non-hydr0gen radicals, then any heteroaryl with less than 3 substitutable positions would be optionally substituted by up to only as many non-hydr0gen radicals as the heteroaryl has substitutable positions To illustrate, tetrazolyl (which has only one substitutable position) would be optionally substituted with up to one non-hydr0gen radical To illustrate further, if an amino nitr0gen is described as being optionally substituted with up to 2 non-hydr0gen radicals, then a primary ammo nitr0gen will be optionally substituted with up to 2 non-hydr0gen radicals, whereas a secondary amino nitr0gen will be optionally substituted with up to only 1 non-hydr0gen radical [0061] This patent application uses the terms substituent and radical interchangeably [0062] The prefix halo indicates that the substituent to which the prefix is attached is substituted with one or more independently selected hal0gen radicals For example, haloalkyl means an alkyl substituent in which at least one hydr0gen radical is replaced with a hal0gen radical Examples of haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 1,1,1-tnfluoroethyl It should be rec0gnized that if a substituent is substituted by more than one hal0gen radical, those hal0gen radicals may be identical or different (unless otherwise stated) [00631 The prefix perhalo indicates that every hydr0gen radical on the substituent to which the prefix is attached is replaced with independently selected hal0gen radicals, i e , each hydr0gen radical on the substituent is replaced with a hal0gen radical If all the hal0gen radicals are identical, the prefix typically will identify the hal0gen radical Thus, for example, the term perfluoro means that every hydr0gen radical on the substituent to which the prefix is attached is substituted with a fluorine radical To illustrate, the term perfluoroalkyl means an alkyl substituent wherein a fluorine radical is in the place of each hydr0gen radical [0064] The term carbonyl (alone or in combination with another term(s)) means -C(O)-[0065] The term ammocarbonyl (alone or in combination with another term(s)) means -C(O)-NH2 [0066] The term oxy (alone or in combination with another term(s)) means an ether substituent, and may be depicted as -0- [0067] The term alkoxy (alone or m combination with another term(s)) means an alkylether substituent, i e , -0-alkyl Examples of such a substituent include methoxy (-0-CH3), ethoxy, n-propoxy, isopropoxy, n-butoxy, is0-butoxy, sec-butoxy, and tert-butoxy [0068] The term alkylcarbonyl (alone or in combination with another term(s)) means -C(O)-alkyl [0069] The term aminoalkylcarbonyl (alone or in combination with another term(s)) means -C(O)-alkyl-NH2 [0070] The term alkoxycarbonyl (alone or in combination with another term(s)) means -C(O)-0-alkyl [0071] The term carbocyclylcarbonyl (alone or in combination with another term(s)) means -C(O)-carbocyclyl [0072] Similarly, the term heterocyclylcarbonyl (alone or in combination with another term(s)) means -C(O)-heterocyclyl [0073] 1 he term carbocyclylalkylcarbonyl (alone or in combination with another term(s)) means -C(O)-alkyl-carbocycly1 [0074] Similarly, the term heterocyclylalkylcarbonyl (alone or in combination with another term(s)) means -C(O)-alkyl-heterocyclyl [0075] The term carbocyclyloxycarbonyl (alone or in combination with another term(s)) means -C(O)- 0-carbocyclyl [0076] The term carbocyclylalkoxycarbonyl (alone or in combination with another term(s)) means -C(O)-0-alkyl-carbocyclyl [0077] The term thio or thia (alone or in combination with another term(s)) means a thiaether substituent, i e , an ether substituent wherein a divalent sulfur atom is in the place of the ether oxygen atom Such a substituent may be depicted as -S- This, for example, alkyl-thi0-alkyl means alkyl-S- alkyl (alkyl-sulfanyl-alkyl) [00781 The term thiol or sulfhydryl (alone or in combination with another term(s)) means a sulfhydryl substituent, and may be depicted as -SH [0079] The term (thiocarbonyl) (alone or in combination with another term(s)) means a carbonyl wherein the oxygen atom has been replaced with a sulfur Such a substituent may be depicted as -C(S)- [0080] The term sulfonyl (alone or in combination with another term(s)) means -S(O)2- [0081] The term aminosulfonyl (alone or in combination with another term(s)) means -S(O)2-NH2 [0082] The term sulflnyl or sulfoxido (alone or in combination with another term(s)) means -S(O)- [0083] The term heterocyclyl (alone or in combination with another term(s)) means a saturated ( e , heterocycloalkyl), partially saturated ( e , heterocycloalkenyl), or completely unsaturated (i e , heteroaryl) ring structure containing a total of 3 to 14 ring atoms Nt least one of the ring atoms is a heteroatom ( e , oxygen, nitr0gen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitr0gen, and sulfur [0084] N heterocyclyl may be a single ring, which typically contains from 3 to 7 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms Examples of single-ring heterocyclyls include furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl (thiofuranyl), dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, tnazolyl, tetrazolyl, oxazolyl, oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazohdinyl, thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5- oxadiazolyl (fiirazanyl), or 1,3,4-oxadiazolyl), oxatnazolyl (including l,2,3,4-oxatriazolyl or 1,2,3,5- oxatriazolyi), dioxazolyl (including l,2,3-dio\azolyl, l,2,4-dioxa7olyl, 1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl, oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl, tetrahydrothiopyranyl, pyndinyl (azinyl), pipendinyl, diazinyl (including pyridazinyl (1,2-diazinyl), pynmidinyl (1,3-diazinyl), or pyrazinyl (1 4-diazmyl)), piperazmyl, tnazinyl (including 1,3,5-triazinyl, 1 2,4-triazinyl and l,2,3-triazmyl)), oxazinyl (including 1,2-oxazinyl, 1,3-oxazinyl, or 1,4-oxazinyl)), oxathiazinyl (including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl, 1,2,5-oxathiazinyl, or 1,2,6-oxathiazinyl)), oxadiazinyl (including 1,2,3-oxadiazinyl, 1,2,4-oxadiazmyl, 1,4,2-oxadiazinyl, or l,3,5-o\adiazinyl)), morpholinyl, azepinyl, oxepinyl, thiepinyl, and diazepinyl [0085] N heterocyclyl alternatively may be 2 or 3 rings fused t0gether, such as, for example, indolizinyl, pyranopyrrolyl, 4H-quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl (including pyndo[3,4-b]-pyndinyl, pyrido[3,2-b]-pyridinyl, or pyndo[4,3-b]-pyridinyl), and ptendinyl Other examples of fused-nng heterocyclyls include benz0-fused heterocyclyls, such as indolyl, isoindolyl (isobenzazolyl, pseudoisomdolyl), indolemnyl (pseudoindolyl), isoindazolyl (benzpyrazolyl), benzazmyl (including quinolinyl (1-benzazinyl) or isoquinolinyl (2-benzazinyl)), phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl (including cmnolinyl (1,2-benzodiazinyl) or quinazolinyl (1,3-benzodiazinyl)), benzopyranyl (including chromanyl or isochromanyl), benzoxazmyl (including 1,3,2-benzoxazinyl, 1,4,2-benzoxazinyl, 2,3,1-benzoxazmyl, or 3,1,4-benzoxazmyl), and benzisoxazinyl (including 1,2-benzisoxazinyl or 1,4-benzisoxazinyl) [0086] The term 2-fused rmg heterocyclyl (alone or in combination with another term(s)) means a saturated, partially saturated, or aryl heterocyclyl containing 2 fused rings Examples of 2-fused-ring heterocyclyls include indolizinyl, quinolizinyl, purinyl, naphthyridinyl, ptendinyl, indolyl, isoindolyl, indolemnyl, isoindazolyl, phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl, benzopyranyl, benzothiopyranyl, benzoxazolyl, anthranilyl, benzodioxolyl, benzodioxanyl, benzoxadiazolyl, benzofuranyl, isobenzofuranyl, benzothiazolyl, benzothiadiazolyl, benzimidazoiyl, benzotnazolyl, benzoxazmyl, and tetrahydroisoquinohnyl [0087[ The term heteroaryl (alone or in combination with another term(s)) means an aromatic heterocyclyl containing from 5 to 14 ring atoms N heteroaryl may be a single ring or 2 or 3 fused nngs Examples of heteroaryl substituents include 6-membered ring substituents such as pyridyl, pyrazyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1,2,4- or 1,2,3-triazinyl, 5-membcred ring substituents such as imidazyl, furanyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-, 1,2,4-, 1,2,5-, or 1,3,4-oxadiazolyl and isothiazolyl, 65-membered fused ring substituents such as benzothiofuranyl, benzisoxazolyl, benzoxazolyl, purinyl, and anthranilyl, and 66-membered fused rings such as benzopyranyl, quinolinyl, isoquinolinyl, cmnolinyl, quinazolinyl, and benzoxazmyl [0088] N prefix attached to a multi-component substituent only applies to the first component To illustrate, the term alkylcycloalkyl contains two components alkyl and cycloalkyl Thus, the C1-C6- prefix on C1-C6-alkyicycloalkyl means that the alkyl component of the alkylcycloalkyl contains from 1 to 6 carbon atoms, the C1-C6-prefix does not describe the cycloalkyl component To illustrate further, the prefix halo on haloalkoxyalkyl indicates that only the alkoxy component of the alkoxyalkyl substituent is substituted with one or more hal0gen radicals If hal0gen substitution may alternatively or additionally occur on the alkyl component, the substituent would instead be described as hal0gen-substituted alkoxyalkyl rather than haloalkoxyalky 1 Nnd finally, if the hal0gen substitution may only occur on the alkyl component, the substituent would instead be described as alkoxyhaloalkyl [0089] If substituents are described as being independently selected from a group, each substituent is selected independent of the other Each substituent therefore may be identical to or different from the other substituent(s) [0090] When words are used to describe a substituent, the rightmost-described component of the substituent is the component that has the free valence [0091] When a chemical formula is used to describe a substituent, the dash on the left side of the formula indicates the portion of the substituent that has the free valence [0092] When a chemical formula is used to describe a linking element between two other elements of a depicted chemical structure, the leftmost dash of the substituent indicates the portion of the substituent that is bound to the left element in the depicted structure The rightmost dash, on the other hand, indicates the portion of the substituent that is bound to the right element m the depicted structure To illustrate, if the depicted chemical structure is X-L-Y and L is described as -C(O)-N(H)-, then the chemical would be X-C(O)-N(H)-y [0093] With reference to the use of the words comprise or comprises or comprising in this patent application (including the claims). Npplicants note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that Npplicants intend each of those words to be so interpreted in construing this patent application, including the claims below [0094] ChemDraw software has been used to generate the compound names in this patent application [0095] The term amorphous as applied to a compound refers to a solid-state m which the compound molecules are present in a disordered arrangement and do not form a distinguishable crystal lattice or unit cell When subjected to X-ray powder diffraction, an amorphous compound does not produce any characteristic crystalline peaks [0096] The term crystalline form as applied to a compound refers to a solid-state in which the compound molecules are arranged to form a distinguishable crystal lattice (i) comprising distinguishable unit cells, and (ii) yielding diffraction pattern peaks when subjected to X-ray radiation [0097[ The term purity, unless otherwise qualified, means the chemical purity of a compound according to conventional HPLC assay [0098] The term phase purity means the solid-state purity of a compound with regard to a particular crystalline or amorphous form of the compound as detei mined by X-ray powder diffraction analytical methods [0099[ The term phase pure refers to purity with respect to other solid-state fonns of the compound, and does not necessarily imply a high degree of chemical purity with respect to other compounds [00100] The term PXRD means X-ray powder diffraction [00101] The term TGN means therm0gravimetnc analysis [00102[The term DSC means differential scanning calorimetry B Compounds [00103] This invention is directed, in part, to compounds that are phenyl-uracil derivatives that correspond in structure to formula I (Formula Removed) is selected from the group consisting of single carbon-carbon bond and [00104] In these compounds, double carbon-carbon bond [00105[ In some embodiments, ---- is a single carbon-carbon bond In these embodiments, the compounds of formula I correspond in structure to the following formula {i e , formula lN) (Formula Removed) [00106[ In other embodiments, ---- is a double carbon-carbon bond In these embodiments, the compounds of formula I correspond in structure to the following formula (i e , formula IB) (Formula Removed) Bl Subtituent R1 [00107] R1 is selected from the group consisting of hydr0gen, methyl, and nitr0gen-protecting group [00108] In some embodiments, R is hydr0gen [00109]In some embodiments, R1 IS methyl [00110] In some embodiments, R1 is selected from the group consisting of hydr0gen and methyl [00111] In some embodiments, R1 is a nitr0gen-protecting group In these embodiments, the compounds are useful as intermediates for the preparation of compounds of formula 1 Nitr0gen-protecting groups suitable for preparing compounds of formula I are known to those skilled in the art B2 Substituent R2 [00112] R2 is selected from the group consisting of hydr0gen, halo, hydroxy, methyl, cyclopropyl, and cyclobutyl [00113] In some embodiments, R2 is hydr0gen [00114] In some embodiments, R2 is halo In some such embodiments, R2 is selected from the group consisting of fluoro and chloro In other such embodiments, R2 is fluoro In yet other such embodiments, R2 is chloro In yet other such embodiments, R2 is bromo In further such embodiments, R2 is lodo [00115] In some embodiments, R2 is hydroxy [00116] In some embodiments, R2 is methyl [00117] In some embodiments, R2 is cyclopropyl [00118] In some embodiments, R2 is cyclobutyl 100119] In some embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, and halo In some such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, fluoro, and chloro In other such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, and fluoro In yet other such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, and chloro In yet other such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, and bromo In further such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, hydroxy, and lodo [00120] In some embodiments, R2 is selected from the group consisting of hydr0gen, methyl, and halo In some such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, fluoro, and chloro In other such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, and fluoro In yet other such embodiments, R2 is selected from the group consisting of hydr0gen, methyl, and chloio In yet other such embodiments, R2 is selected from the group consisting o< hydr0gen, methyl and bromo In further such embodiments, R2 is selected from the group consisting of hydr0gen methyl, and lodo [00121] In some embodiments, R2 is selected from the group consisting of hydr0gen and halo In some such embodiments, R2 is selected from the group consisting of hydr0gen, fluoro, and chloro In other such embodiments, R2 is selected from the group consisting of hydr0gen and fluoro In yet other such embodiments, R2 is selected from the group consisting of hydr0gen and chloro In yet other such embodiments, R2 is selected from the group consisting of hydr0gen and bromo In further such embodiments, R2 is selected from the group consisting of hydr0gen and lodo B3 Subslituent R3 [00122] R2 is selected from the group consisting of hydr0gen, halo, oxo, and methyl In some such embodiments, R3 is selected from the group consisting of hydr0gen, fluoro, oxo, and methyl In other such embodiments, R3 is selected from the group consisting of hydr0gen, chloro, oxo, and methyl In yet other such embodiments, R3 is selected from the group consisting of hydr0gen, bromo, oxo, and methyl In yet other such embodiments, R3 IS selected from the group consistmg of hydr0gen, lodo, oxo, and methyl [00123] In some embodiments, R3 IS selected from the group consisting of hydr0gen, halo, and oxo In some such embodiments, R3 IS selected from the group consisting of hydr0gen, fluoro, and oxo In other such embodiments, R3 is selected from the group consisting of hydr0gen, chloro, and oxo In yet other such embodiments, R3 is selected from the group consisting of hydr0gen, bromo, and oxo In yet other such embodiments, R3 is selected from the group consisting of hydr0gen, lodo, and oxo [00124] In some embodiments, R3 is selected from the group consisting of hydr0gen and methyl [00125] In some embodiments, R2 is hydr0gen [00126] In some embodiments, R2 is methyl [00127] In some embodiments, R2 is oxo [00128] In some embodiments, R2 is halo in some such embodiments, R2 is fluoro In other such embodiments, R1 IS chloro In yet other such embodiments, R1 is bromo In further such embodiments, R3 IS lodo B4 SubsUtuent R4 100129] R1 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, -wherein (a) the amino aminocarbonyl, and aminosulfonyl optionally are substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, or (2) two substituents that, t0gether with the ammo nitr0gen, form a single-ring heterocyclyl, (b) the alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, and alkylsulfonyl, optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, ammo, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, t0gether with the ammo nitr0gen, form a single-ring heterocyclyl, and (c) the carbocyclyl and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, 0X0, nitro, cyano, azido, hydroxy, amino, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the ammo optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, t0gether with the amino nitr0gen, form a single-ring heterocyclyl [00130] In some embodiments, R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, ammo, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, wherein the amino, aminocarbonyl, and aminosulfonyl optionally are substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, or (2) two substituents that, t0gether with the ammo nitr0gen, fonn a single-ring heterocyclyl [00131] In some embodiments, R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azrdo, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, and alkylsulfonyl, optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyi, and heterocyclylalkyl, or (2) two substituents that, t0gether with the amino nitr0gen, form a single-ring heterocyclyl [00132] In some embodiments R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, ammo, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, wherein the carbocyclyl and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyi, and heterocyclylalkyl, or (2) two substituents that, t0gether with the ammo nitr0gen, form a single-rmg heterocyclyl [00133] In some embodiments, R is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, ammo, aminocarbonyl, aminosulfonyl. alkyisulfonyl, carbocyclyi, and heterocyclyl, wherein (a) the amino, aminocarbonyl, and aminosulfonyl optionally are substituted with (1) one or two substituents independently selected from the group consisting of alkyl, aikenyl, and alkynyl, or, (2) two substituents that, t0gether with the amino nitr0gen, form a single-nng heterocyclyl, and (b) the alkyl, aikenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyl, carbocyclyi, and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, carbocyclyi, and heterocyclyl, wherein the amino optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, aikenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyi, heterocyclyl, carbocyclylalkyi, and heterocyclylalkyi, or, (2) two substituents that, t0gether with the ammo nitr0gen, form a smgle-nng heterocyclyl [00134] In some embodiments, R4 is selected from the group consisting of halo, alkyl, aikenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyi, and heterocyclyl, wherein the amino, aminocarbonyl, and aminosulfonyl optionally are substituted with (1) one or two substituents independently selected from the group consisting of alkyl, aikenyl, and alkynyl, or, (2) two substituents that, t0gether with the amino nitr0gen, form a single-nng heterocyclyl [00135] In some embodiments, R4 is selected from the group consisting of halo, alkyl, aikenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyi, and heterocyclyl, wherein the alkyl, aikenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyl, carbocyclyi, and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, carbocyclyi, and heterocyclyl, wherein the ammo optionally is substituted with (1) one or two substituents independently selected from the group consisting of alkyl, aikenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyi, heterocyclyl, carbocyclylalkyi, and heterocyclylalkyi, or, (2) two substituents that, t0gether with the amino nitr0gen, form a smgle-nng heterocyclyl [00136] In some embodiments, R4 is selected from the group consisting of halo, C1-C2-alkyI, C2-C4-alkenyl, C2-C4-alkynyl, amino C1-C4-alkylsullonyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl wherein (a) the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, (b) the C1-C4-aIkyl, C2-C4-alkenyl, and C2-C4-alkynyl optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and tnmethylsilyl, and (c) the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, and amino, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl [00137] In some embodiments, R4 is selected from the group consisting of C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein (a) the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, (b) the C1-C4-alkyl, C2-C4-alkenyl, and C2-C4-alkynyl optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and tnmethylsilyl, and (c) the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, and amino, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl [00138] In some embodiments, R4 is selected from the group consisting of halo, C1-C4-alkyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and tnmethylsilyl, and (b) the C1-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylammo [00139] In some embodiments, R4 is selected from the group consisting of halo, C1-C4-alkyl, C3-C6- carbocyclyl, and 5-6-membered heterocyclyl, wherein (a) the C1-C4-alkyl optionally is substituted with one or two substituents independently selected from the group consisting of halo oxo, hydroxy, alkyloxy, and trimethylsilyl, and (b) the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with a substituent selected from the group consisting of alkyl, halo, and alkylsulfonvlamino [00140] In some embodiments, R2 is selected from the group consisting of C1-C4-alkyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and trimethylsilyl, and (b) the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylamino [00141] In some embodiments, R4 is selected from the group consisting of halo, tert-butyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with a substituent selected from the group consisting of alkyl, halo, and alkylsulfonylamino [00142] In some embodiments, R4 is selected from the group consisting of tert-butyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with a substituent selected from the group consisting of alkyl, halo, and alkylsulfonylamino [00143] In some embodiments, R4 is selected from the group consistmg of halo, alkyl, haloalkyl, carboxyalkyl, hydroxyalkyl, alkyloxyalkyl, trimethylsilylalkynyl, alkylcarbocyclyl, carbocyclyl, alkylheterocyclyl, heterocyclyl, halocarbocyclyl, alkylsulfonylamino, and alkylsulfonyl [00144] In some embodiments, R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, ammocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl [00145] In some embodiments, R4 is selected from the group consisting of halo, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, ammo, C1-C4-alkylsulfonyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiment, R4 is selected from the group consisting of halo, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, C6-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiment, R4 is selected from the group consisting of halo, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, phenyl, and 5-6-membered heteroaryl [00146] In some embodiments, R4 is selected from the group consistmg of C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiment, R4 is selected from the group consisting of C]-C4-alkyl C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, Ce-carbocyciyl, and 5-6-membered heterocyclyl In other such embodiment, R4 is selected from the group consisting of C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, amino, C1-C4-alkylsulfonyl, phenyl and 5-6-membered heteroaryl [00147] In some embodiments, R2 is selected from the group consistmg of halo, C1-C4-alkyl, CrC6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiments, R is selected from the group consisting of halo, C1-C4-alkyl, Cg-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiments, R4 is selected from the group consisting of halo, C1-C4-alkyl, phenyl, and 5-6-membered heteroaryl [00148) In some embodiments, R4 is selected from the group consisting of C1-C4-alkyl C3-C6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiments, R is selected from the group consisting of C1-C4-alkyl, C6-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiments, R4 is selected from the group consistmg of C1-C4-alkyl, phenyl, and 5-6-membered heteroaryl [00149] In some embodiments, R4 is selected from the group consistmg of halo, tert-butyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiments, R4 is selected from the group consisting of halo, tert-butyl, C6-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiments, R4 is selected from the group consisting of halo, tert-butyl, phenyl, and 5-6-membered heteroaryl [00150] In some embodiments, R4 is selected from the group consisting of tert-butyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl In some such embodiments, R4 is selected from the group consisting of tert-butyl, C6-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiments, R4 is selected from the group consisting of tert-butyl, phenyl, and 5-6-membered heteroaryl [00151] In some embodiments, R4 is selected from the group consisting of C3-C6-carbocyclyl and 5-6-membered heterocyclyl In some such embodiments, R4 is selected from the group consisting of C6-carbocyclyl, and 5-6-membered heterocyclyl In other such embodiments, R4 is selected from the group consisting of phenyl and 5-6-membered heteroaryl [00152] Suitable carbocyclyls for the above embodiments include, for example, cyclopropyl and phenyl [00153] Suitable heterocyclyls for the above embodiments include, for example, furanyl, thienyl, and pyridinyl [00154] In some embodiments, R4 is selected from the group consisting of halo, alkyl, and alkyloxy [00155] In some embodiments, R4 is alkyl [00156] In some embodiments, R4 is tert-butyl B5 Substituent R2 [00157] R1 IS selected from the group consisting of hydr0gen, hydroxy, alkyl, alkenyl, alkynyl, alkyloxy. alkenyloxy, alkynyloxy, alkylsulfonyloxy, carbocyclylsulfonyloxy, haloalkylsulfonyloxy, and halo [00158] In some embodiments, R1 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and halo In some such embodiments, R4 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and fluoro In other such embodiments R5 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and fluoro In yet other such embodiments, R5 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and chloro In yet other such embodiments, R5 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and bromo In further such embodiments, R is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and lodo [00159] In some embodiments, R1 is selected from the group consisting of hydr0gen, hydroxy, methoxy, and halo In some such embodiments, R is selected from the group consisting of hydr0gen, hydroxy, methoxy, and fluoro In other such embodiments, R2 is selected from the group consisting of hydr0gen, hydroxy, methoxy, and chloro In yet other such embodiments, R1 IS selected from the group consisting of hydr0gen, hydroxy, methoxy, and bromo In further such embodiments, R is selected from the group consisting of hydr0gen, hydroxy, methoxy, and lodo [00160] In some embodiments, R1 is selected from the group consisting of hydr0gen, hydroxy, and alkyloxy In some such embodiments, R1 IS selected from the group consisting of hydr0gen, hydroxy, methoxy, and ethoxy [00161] In some embodiments, R1 IS S hydr0gen [00162] In some embodiments, R1 IS hydroxy [00163] In some embodiments, R1 is alkyloxy [00164] In some embodiments, R4 is methoxy [00165[ In some embodiments, R4 is ethoxy B6 Substituent L [00166] L is a bond, and the compounds of formula I correspond in structure to formula I-LO (Formula Removed) [00167[In some such embodiments, the compounds correspond in structure to the following formula ( e , formula lN-LO) (Formula Removed) [00168] In other such embodiments, the compounds correspond in structure to the following formula ( e formula EB-LO) (Formula Removed) B7 Substituent R2 [00169] In some embodiments, R4 is selected from the group consisting of fused 2-nng carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of RE, R4, R2, RH, R1, RJ, and RK [00170] In some such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are not substituted [00171] In other such embodiments, the fused 2-ring carbocyclyl and fused 2-rmg heterocyclyl are substituted with a substituent selected from the group consisting of R2, , R2, R, R1, R1, and R4 In some such embodiments, the fused 2-nng carbocyclyl and fused 2-ring heterocyclyl are substituted with a substituent selected from the group consisting of R1, B, R1, R1, and R1 In other such embodiments, fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with a substituent selected from the group consisting of R2, R4, and R1 In yet other such embodiments, the fused 2-nng carbocyclyl and fused 2-ring heterocyclyl are substituted with a substituent selected from the group consisting of R4 and R1 In other such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with R- [00172] In yet other such embodiments, the ftised 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with two substituents independently selected from the group consisting of R2, R4, R2, R, R1, R-, andR- In some such embodiments, the fiised 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with two substituents independently selected from the group consisting of R2, R1, R\ R1, and R In other such embodiments, the fused 2-nng carbocyclyl and fused 2-ring heterocyclyl are substituted with two substituents independently selected from the group consisting of R , R , and R In other such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with two substituents independently selected from the group consisting of R and R [00173] In further such embodiments, the fiised 2-ring carbocyclyl and fused 2-rmg heterocyclyl arc substituted with three substituents independently selected from the group consisting of R R R , R , R, R1, and R4 In some such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with three substituents independently selected from the group consisting of R , R , R , R , and R In other such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with three substituents independently selected from the group consisting of R , R , and R In further such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with three substituents independently selected from the group consisting of R and R [00174] In further such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with one, two, or three substituents independently selected from the group consisting of R , R4, R2, R, R1, R1, and R1 In some such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with one, two, or three substituents independently selected from the group consisting of R4, R, R1, R1, and R2 In other such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with one, two, or three substituents independently selected from the group consisting of R2, R1, and R1 In further such embodiments, the fused 2-ring carbocyclyl and fused 2-ring heterocyclyl are substituted with one, two, or three substituents independently selected from the group consisting of R4 and R1 [00175] In some embodiments, R4 is fused 2-ring carbocyclyl optionally substituted with one or more substituents independently selected from the group consisting of R4, R2, R4, R, R1, R1, and R4 In some such embodiments, the fused 2-ring carbocyclyl is not substituted In other such embodiments, the fused 2-ring carbocyclyl is substituted with a substituent selected from the group consisting of R1, R1, R2, R, R1, R1, and R4 In yet other such embodiments, the fused 2-nng carbocyclyl is substituted with two substituents independently selected from the group consisting of R2, R4, R4, R, R1, R1, and R4 In further such embodiments, the fused 2-ring carbocyclyl is substituted with three substituents independently selected from the group consisting of R2, R2, R2, R, R1, R, and R2 In further such embodiments, the fiised 2-ring carbocyclyl is substituted with one, two, or three substituents independently selected from the group consisting of R2, R, R4, R, R, R1, and R1 [00176] In some embodiments, R1 IS fused 2-ring heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of R4, R4, R4, R, R1, R1, and R4 In some such embodiments, the fused 2-ring heterocyclyl is not substituted In other such embodiments, the fused 2-ring heterocyclyl is substituted with a substituent selected from the group consisting of R2, R1, 4, R, R\ R1, and R1 In yet other such embodiments, the fused 2-ring heterocyclyl is substituted with two substituents independently selected from the group consisting of R4, R, R1, R, R1, R1, and R2 In further such embodiments, the fused 2-ring heterocyclyl is substituted with three substituents independently selected from the gioup consisting of R4, R4, R4, R, R1, R1, and R In further such embodiments the fused 2-ring heterocyclyl is substituted with one, two, or three substituents independently selected from the group consisting of R2, R2, R4, R, R1, R1, and R4 [00177] In some of the above embodiments, the optionally substituted fused 2-ring carbocyclyl is selected trom the group consisting of naphthalenyl, dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl, decahydronaphthalenyl, indenyl, dihydroindenyl, hexahydroindenyl, octahydroindenyl, pentalenyl, octahydropentalenyl, and hexahydropentalenyl In some such embodiments, the optionally substituted fused 2-ring carbocyclyl is selected from the group consisting of naphthalenyl and dihydroindenyl In some such embodiments, the optionally substituted fused 2-ring carbocyclyl is naphthalenyl In other such embodiments, the optionally substituted fused 2-ring carbocyclyl is dihydroindenyl In further such embodiments, the optionally substituted fused 2-nng carbocyclyl is indenyl [001781 some of the above embodiments, the optionally substituted fused 2-rmg heterocyclyl is selected from the group consisting of (Formula Removed) X, X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S, X X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S, X is selected from the group consisting of N(H), O, and S, X, X, X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S, X X, X, and X are independently selected from the group consisting of N and C(H), one or more of X, X, and X is N, and the remaining one(s) isare C(H), one or more of X X, X, and X is N, and the remaining one(s) isare C(H), 28 one or more of X ,X and X is N, and the remaining one(s) isare C(H), ne or more of X, X, X, and X is N, and the remaining one(s) isare C(H), one or more of X, X, and X is N, and the remaining one(s) isare C(H), one or more of X, X, X, and X is N, and the remaining one(s) isare C(H), X, X, and X are mdependently selected from the group consisting of N and C(H), one of X, X, and X is selected from the group consisting of N(H) O, and S, and the remaining two are C(H)2, one of X and X is selected from the group consisting of N(H), O and S, and the other one is C(H)2, X, X, X, and X are independently selected from the group consisting of N and C(H), X, X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S, X, X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S X is selected from the group consisting of isI(H), O, and S, X, X, X, and X are independently selected from the group consisting of N and C(H), X is selected from the group consisting of N(H), O, and S, X , X, X, and X are independently selected from the group consisting of N and C(H), one or more of X™, X, and X is N, and the remaining one(s) isare C(H), one or more of X, X, X, and X is N, and the remaining one(s) isare C(H), and one of X and X is N(H), and the remaining one is C(H)2 [00179] In some of the above embodiments, the optionally substituted fused 2-ring heterocyclyl is selected from the group consisting of [00180] In some of the above embodiments, the optionally substituted fused 2-ring heterocyclyl is selected from the group consisting of (Formula Removed) [00181] In some of the above embodiments, X, X, and X are C(H) [00182] In some of the above embodiments, X X, and X are C(H) [00183] In some of the above embodiments, X, X, X\ and X are C(H) [00184] In some of the above embodiments, X X, X, and X are C(H) [00185[ In some of the above embodiments, one of X, X, and X is N [00186[ In some of the above embodiments, one of X, X, X\ and X is N [00187] In some of the above embodiments, one of X , X, and X is N, and one of X , X, X, and X is N [00188] In some of the above embodiments, X, X, and X are C(H) [00189[In some of the above embodiments, X, X, X, and X are C(H) [00190] In some of the above embodiments, x, X and X are C(H) [00191] In some of the above embodiments, X, X, and X are C(H) 100192] In some of the above embodiments, X\ X, X, and X are C(H) [00193] In some of the above embodiments, X, X, X, and X are C(H) [00194] In some of the above embodiments, one or more of X™, X\ and X is N, and the remaining one(s) isare C(H) [00195] In some of the above embodiments, one or more of X, X X, and X is N, and the remaining one(s) isare C(H) B8 Substituent R2 [00196] Each R2 is independently selected from the group consisting of halo, nrtro, hydroxy, oxo, carboxy, cyano, amino, imino, azido, and aldehydo, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl [00197] In some embodiment, each R2 is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, amino, immo, and aldehydo, wherein the amino optionally is substituted with one or two independently selected alkyl [00198] In some embodiment, each R2 is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, amino, imino, aldehydo, and alkylamino [00199] In some embodiment, each R4 is independently selected from the group consisting of chloro, fluoro, nitro, hydroxy, oxo, carboxy, amino, imino, aldehydo, and alkylamino [00200] In some embodiment each R4 is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, cyano, amino, imino, and azido In some such embodiments, each R is halo In other such embodiments, each R4 is nitro In yet other such embodiments, each R is hvdroxy In yet other such embodiments, each R4 is oxo In yet other such embodiments, each R is carboxy In yet other such embodiments, each R2 is cyano In yet other such embodiments, each R is ammo In further such embodiments, each R1 IS immo In yet further such embodiments, each R is and azido [00201] In some embodiments, each R4 is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, cyano, amino, and imino B9 Substituent R1 [00202] Each R4 is independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, azido, 0X0, aminosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the ammo, imino, aminosulfonyl, aminocarbonyl, carbocyclyl, and heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, alkylsulfonylamino, hydroxy, and alkyloxy, wherein amino portion of the alkylsulfonylamino optionally is substituted with a substituent selected from the group consisting of alkyl, alkenyl, and alkynyl [00203] In some embodiment, each R2 is independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, immo, nitro, azido, 0X0, aminosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the ammo, imino, aminosulfonyl, and aminocarbony! optionally are substituted with one or tvvo substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, and alkylsultonylamino, wherein amino portion of the alkylsultonylamino optionally is substituted with a substituent selected from the group consisting of alkyl, alkenyl, and alkynyl [00204] In some of the above embodiments each R4 is independently selected from the group consisting of the alkyl alkynyl, and alkynyl, wherein such substituents are not substituted [00205] In some embodiments, each R2 is independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein each such substituent optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, oxo, aminosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, imino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkylsulfonyl, and alkylsulfonylamino, wherein ammo portion of the alkylsulfonylamino optionally is substituted with alkyl [00206] In some embodiments, each R1 is an independently selected alkyl optionally substituted with a substituent selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, oxo, aminosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, imino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkylsulfonyl, and alkylsulfonylamino, wherein amino portion of the alkylsulfonylamino optionally is substituted with alkyl [00207] In some embodiments, each R2 is an independently selected alkyl optionally substituted with a substituent selected from the group consisting of carboxy, halo, ammo, imino, and aminosulfonyl, wherein the amino, imino, and aminosulfonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkylsulfonyl, and alkylsulfonylamino [00208] In some embodiments, each R1 is an independently selected alkyl optionally substituted with amino, wherein the amino optionally is substituted with alkylsulfonyl [00209] In some embodiments, each R4 is an independently selected alkyl substituted with amino, wherein the amino is substituted with alkvlsulfonyl In some such embodiments, each R is methylsulfonylaminomethyl [00210] In some embodiments each R1 IS independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein each such substituent optionally is substituted with one, two, or three substituents independently selected from the group consisting ol carboxy, hydroxy, halo, amino, imino, nitro, azido, 0X0, ammosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl [00211] In some embodiments, each R1 IS independently selected alkyl substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, azido, oxo, ammosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl BIO Substituent R° [00212] Each R2 is independently selected from the group consisting of carbocyclyl and heterocyclyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, halo, amino, nitro, azido, oxo, ammosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, ammosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl [00213] In some of the above embodiments, each R2 is independently selected from the group consisting of carbocyclyl and heterocyclyl, wherein such substituents are not substituted [00214] In some embodiments, each R2 is independently selected from the group consisting of carbocyclyl and heterocyclyl, wherein each such substituent optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, halo, amino, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, aminosulfonyl, and aminocarbonyl optionalIj- are substituted with one or two substituents independently selected from the group consisting of alkyl and alkylsulfonyl [00215] In some of the above embodiments, the carbocyclyl is Cs-Ca-carbocyclyl [00216] In some of the above embodiments, the heterocyclyl is 5-6-membered heterocyclyl Bll Substituent R [00217] Each R IS independently selected from the group consisting of alkyloxy, alkenyloxy, alkynyloxy, aikylsulfonyloxy, alkenylsulfonyloxy, and alkynylsulfonyloxy, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, 0X0, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl [00218] In some of the above embodiments, each R IS independently selected from the group consisting of alkyloxy, alkenyloxy, alkynyloxy, aikylsulfonyloxy, alkenylsulfonyloxy, and alkynylsulfonyloxy, wherein such substituents are not substituted [00219] In some embodiments, each R IS independently selected from the group consisting of alkyloxy and aikylsulfonyloxy, wherein each such substituent optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl and alkylsulfonyl [00220] In some embodiments, each R IS independently selected from the group consisting of alkyloxy and aikylsulfonyloxy, wherein each such substituent optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, oxo, aminosulfonyl. alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, cyano, and ammocarbonyl, wherein the ammo, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl and alk-ylsulfonyl [00221] In some embodiments, each R IS independently selected from the group consisting of alkyloxy and alkylsulfonyloxy, wherein each such substituent optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, 0X0, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, cyano, and aminocarbonyl [00222] In some embodiments, each R is independently selected alkyloxy [00223] In some embodiments, each R4 is independently selected alkylsulfonyloxy B12 Substituent R1 [00224] Each R1 IS independently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, aminocarbonyl, alkyloxycarbonyl, carbocyclylcarbonyl, and heterocyclylcarbonyi, wherein (a) the alkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the ammocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxyalkyl, carbocyclyl, heterocyclyl, alkylsulfonyl, and alkylsulfonylamino, wherein the carbocyclyl and heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of halo, alkyl, and oxo [00225] In some embodiments, each R1 IS mdependently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, aminocarbonyl, alkyloxycarbonyl, carbocyclylcarbonyl, and heterocyclylcarbonyi, wherein such substituents are not substituted [00226] In some embodiments, each R1 is independently selected from the group consisting of alkylcarbonyl, aminocarbonyl, alkyloxycarbonyl, carbocyclylcarbonyl, and heterocyclylcarbonyi, wherein (a) the alkylcarbonyl optionally is substituted with a substituent selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with a substituent selected from the group consisting of alkyl alkyloxyalkyl, alkylsulfonyl, and alkyisulfonylamino [00227] In some embodiments each R1 is independently selected from the group consisting oi alkylcarbonyl and aminocarbonyl, wherein the aminocarbonyl optionally is substituted with a substituent selected from the group consisting of alkyl, alkyloxyalkyl, alkylsulfonyl, and alkylsulfonylammo [00228] In some embodiment, each R1 IS independently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl alkynylcarbonyl, and aminocarbonyl, wherein (a) the alkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonylammo [00229] In some of the above embodiments, each R1 IS independently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, and aminocarbonyl, wherein such substituents are not substituted [00230] In some embodiments, each R1 IS independently selected from the group consisting of alkylcarbonyl and aminocarbonyl, wherein (a) the alkylcarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkylsulfonylammo [00231] In some embodiments, each R1 IS independently selected from the group consisting of alkylcarbonyl and aminocarbonyl, wherein (a) the alkylcarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, cyano, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alky! and alkylsulfonylamino [00232] In some embodiments, each R1 IS independently selected from the group consisting of alkylcarbonyl and aminocarbonyl, wherein the alkylcarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo amino nitro, aztdo, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl [00233] In some embodiments, each R1 IS independently selected alkylcarbonyl [00234] In some embodiments, each R1 is independently selected aminocarbonyl B13 Suhstituent R J002351 Each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, alkyloxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylammo, alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, aminocarbonylamino, alkyloxycarbonylaminoimino, alkylsulfonylaminoimino, alkenylsulfonylammoimino, and alkynylsulfonylaminoimino, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkenyl, alkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, halo, 0X0, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, and alkynyloxy, wherem the alkyl optionally is substituted with one or more hydroxy, (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or more substituents independently selected from the group consisting of alkyl alkenyl, alkynyl, caiboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy halo nitro, cyano, azido, and amino, wherein the amino optionally is substituted with one or two substituents independently selected from the group consistmg of alkyl, alkenyl, and alkynyl [00236] In some embodiment, each R1 IS independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, alkyloxycarbonylamino, alkcnyloxycarbonylamino, alkynyloxycarbonylamino, alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, aminocarbonylamino, alkylsulfonylaminoimmo, alkenylsulfonylaminoimino, and alkynylsulfonylaminoimino, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkenyl, alkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, halo, oxo, ammo, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, and alkynyloxy, wherein the alkyl optionally is substituted with one or more hydroxy, (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or more substituents independently selected from the group consisting of alky I, alkenyl, alkynyl, carboxy, hydro\y, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, and amino wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, and [00237] In some of the above embodiments, each R1 IS independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylammo, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, alkyloxycarbonylamino, alkenyloxycarbonylamino, aikynyloxycarbonylamino, alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylammo, aminocarbonylamino, alkylsulfonylaminoimino, alkenylsulfonylaminoimino, and alkynylsulfonylaminoimino, wherein such substituents are not substituted [00238] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylammo, alkylcarbonylamino, alkyloxycarbonylamino, alkylsulfonylamino, aminocarbonylamino, and alkylsulfonylaminoimino, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and ammo, and (2) the ammo portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, ammo, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy, (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloty, halo nitro, cyano, and ammo, wherein the amino optionally is substituted with one or two substituents independently selected alkvl [00239] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylsulfonylamino, and alkylsulfonylaminoimmo, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy, (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, and amino, wherein the ammo optionally is substituted with one or two substituents independently selected alkyl [00240] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylsulfonylamino, and alkylsulfonylaminoimmo, wherein the ammo portion of such substituents optionally is substituted with a substituent dependently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkylo\yaIkylo\ycarbony 1, alkylcarbonyloKyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy halo, nitro, cyano, oxo, and amino, and (2) the ammo portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl [00241] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylsulfonylamino, and alkylsulfonylaminoimino, wherein the alkyl portion of the alkylsulfonylamino and alkylsulfonylaminoimino optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, ammo, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents mdependently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00242] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylsulfonylamino, and alkylsulfonylaminoimino, wherein the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, and amino [00243] In some embodiments, each R1 is independently selected from the group consisting of carbocyclylsulfonylamino and heterocyclylsulfonylamino, wherein the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or two substituents mdependently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, and ammo [00244] In some embodiments, each R1 IS independently selected from the group consisting of alkylsulfonylamino, alkenylsulfonylammo, alkynylsulfonylammo, and alkylsulfonylaminoimino, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyi heterocyclylalkyl, alkylcarbonyloxy, ammocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alk\loxyalkyloxycarbonyl, alkylcarbonyloxyalkyl and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyi and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl carboxy, hydroxy alkyloxy halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the ammocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, 0X0, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00245] In some embodiments, each R1 is an independently selected alkylsulfonylammo, wherein (a) the amino portion of the alkylsulfonylammo optionally is substituted with a substituent mdependently selected from the group consisting of carbocyclylalkyi, heterocyclylalkyl, alkylcarbonyloxy, ammocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyi and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the ammocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl portion of the alkylsulfonylammo optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00246] In some embodiments, each R1 is an independently selected alkylsulfonylammo wherein the amino portion of the alkylsulfonylammo optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyi, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylaikyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherem (1) the carbocyclyl portion of the carbocyclylalkyi and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and ammo, and (2) the ammo portion of the aminocarbonylaikyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl [00247] In some embodiments, each R1 is an mdependently selected alkylsulfonylammo, wherein the amino portion of the alkylsulfonylammo optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyi, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylaikyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl [00248] In some embodiments, each R1 is an independently selected alkylsulfonylammo, wherein the alkyl portion of the alkylsulfonylammo optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the ammo optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00249] In some embodiments, each R1 IS an independently selected alkylsulfonylammo, wherein the alkyl portion of the alkylsulfonylammo optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano [00250] In some embodiments, each R1 is an independently selected alkylsulfonylammo In some such embodiments, each R1 is methylsulfonylamino [00251] In some embodiments, each R1 is an independently selected alkylsulfonylammoimmo, wherein (a) the amino portion of the alkylsulfonylammoimmo optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl heterocyclyIalkyl, alWylcarbonyloxy aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkylo\yalkyloxycarbonyl, alkylcarbonjloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl portion of the alkylsulfonylammoimmo optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00252] In some embodiments, each R1 is an independently selected alkylsulfonylammoimmo, wherein the amino portion of the alkylsulfonylammoimmo optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl [00253] In some embodiments, each R1 IS an independently selected alkylsulfonylammoimmo, wherein the ammo portion of the alkylsulfonylammoimmo optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl alkylcarbonyloxy, ammocarbonylalkyi, aikyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl [00254] In some embodiments, each R1 IS an independently selected alkylsulfonylammoimmo, wherein the alkyl portion of the alkylsulfonylammoimmo optionalK is substituted with one or two substituents independently selected from the group consisting ot carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents mdependently selected from the group consisting of alkyl and alkyloxy, wherein the alkyl optionally is substituted with one or more hydroxy [00255] In some embodiments, each R1 is an independently selected alkylsulfonylammoimmo, wherein the alkyl portion of the alkylsulfonylammoimmo optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano [00256] In some embodiments, each R1 is an independently selected alkylsulfonylammoimmo In some such embodiments, each R1 is methylsulfonylaminoimino [00257] In some embodiments, each R1 is independently selected from the group consisting of alkylcarbonylamino and alkyloxycarbonylamino, wherein the alkyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, ammo, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano B14 Substituent R1 [00258] Each R4 is independently selected from the group consisting of aminosulfonyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl, wherein (a) the alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, ammo, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl [00259] In some of the above embodiments each R4 is independently selected from the group consisting of aminosulfonyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl, wherein such substituents are not substituted [00260] In some embodiments each R4 is independently selected from the group consisting of aminosultonyl and alkylsulfonyl, wherein (a) the alkylsulfonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino nitro, oxo aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected aikyl [00261] In some embodiments, each R4 is independently selected from the group consisting of aminosulfonyl and alkylsulfonyl C Embodiments of Compounds of Formula I [00262] Various embodiments of substituents R1, R2 R2 R4, R2 L, R, R, R4, R°, R4, R2, R4, R1, R, R1, R1, and R4 have been discussed above These substituent embodiments can be combined to form various embodiments of compounds of formula I Nll embodiments of compounds of formula I formed by combining the substituent embodiments discussed above are within the scope of Npplicants invention, and some illustrative embodiments of the compounds of formula I are provided below [00263] In some embodiments, the compounds of formula I correspond in structure to formula I-LO (Formula Removed) is selected from the group consisting of single carbon-carbon bond and double carbon-carbon bond, R is selected from the group consisting of hydr0gen and methyl, R2 is selected from the group consisting of hydr0gen and halo R is selected from the group consisting of hydr0gen and halo, R4 is selected from the group consisting of C1-C4-alkyl, Ca-Ce-carbocycIyl, and 5-6-membered heterocyclyl, wherein (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo oxo hydroxy, alkyloxy, and trimethylsilyl and (b) the Cs-Ce-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylamino R2 is selected from the group consisting of hydr0gen, hydroxy, alkyloxy, and halo, R4 is selected from the group consisting of fused 2-ring heterocyclyl and fused 2-ring carbocyclyl, wherein each such substituent is substituted with one, two, or three substituents independently selected from the group consisting of R , R , R , R , and R , each R2 is independently selected from the group consisting of chloro, fluoro, nitro, hydroxy, oxo, carboxy, amino, imino, aldehydo, and alkylamino, each R1 IS an independently selected alkyl optionally substituted with a substituent selected from the group consisting of carboxy, halo, amino, imino, and aminosulfonyl, wherein the ammo, imino, and aminosulfonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkylsulfonyl, and alkylsulfonylamino, each R1 IS independently selected from the group consisting of alkylcarbonyl and aminocarbonyl, wherein the aminocarbonyl optionally is substituted with a substituent selected from the group consistmg of alkyl, alkyloxyalkyl, alkylsulfonyl, and alkylsulfonylammo, each R1 is independently selected from the group consisting of alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, and alkylsulfonylaminoimino, wherein (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyi, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyi optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl. (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherem the alkyl optionally is substituted with one or more hydroxy, and each R4 is independently selected from the group consisting of aminosulfonyl and alkylsulfonyl, wherein (a) the alkylsulfonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected alkyl [00264] In some embodiments, the compounds of formula I correspond in structure to formula I-LO (Formula Removed) is selected from the group consisting of single carbon-carbon bond and double carbon-carbon bond, R1 is hydr0gen, R is selected from the group consisting of hydr0gen and halo R2 is hydr0gen, R IS tert-butyl, R is selected from the group consisting of hydr0gen, hydroxy, methoxy, and halo, R IS a fused 2-ring carbocyclyl selected from the group consisting of naphthalenyl, dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl, decahydronaphthalenyl, indenyl, dihydroindenyl, hexahydroindenyl, octahydroindenyl, pentalenyl, octahydropentalenyl, and hexahydropentalenyl, wherein each such substituent is substituted with a substituent selected from the group consisting of R and R1 R1 IS alkylsulfonylaminoalkyl, and R1 IS alkylsulfonylamino [00265] Examples of compounds of formula I (and salts thereof) are shown in Tables 1-9 below I he synthesis examples below provide step-by-step preparation instructions for some of these compounds The remaining compounds were prepared utilizing the general method-of-preparation discussion, specific synthesis examples below, andor the discussion throughout this application (Table Removed) D Isomers [00266] This invention also is directed, in part, to all isomers of the compounds of formula I (and their salts) ( e , structural and stereoisomers) Structural isomers include chain and position isomers Stereoisomers include EZ isomers ( e , isomers with regard to one or more double bonds), enantiomers ( e , stere0- isomers that have opposite configurations at all stere0genic centers), and diastereoisomers ( e , stere0- isomers that have the same configuration at one or more stere0genic centers, but differ at other stere0genic centers) E Salts [00267] This invention also is directed, in part, to all salts of the compounds of formula I N salt of a compound may be advantageous due to one or more of the salts properties, such as, for example, enhanced pharmaceutical stability m differing temperatures and humidities, or a desirable solubility in water or other solvents Where a salt is intended to be administered to a patient (as opposed to, for example, being in use in an m vitro context), the salt preferably is pharmaceutically acceptable andor physiol0gically compatible The term pharmaceutically acceptable is used adjectivally in this patent application to mean that the modified noun is appropriate for use as a pharmaceutical product or as a part of a pharmaceutical product Pharmaceutically acceptable salts include salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases In general, these salts typically may be prepared by conventional means by reacting, for example, the appropriate acid or base with a compound of the invention [00268] Pharmaceutically acceptable acid addition salts of the compounds of formula I can be prepared from an inorganic or organic acid Examples of often suitable inorganic acids include hydrochloric, hydrobr0mlc, hydroiodic, nitric carbonic, sulfuric, and phosphoric acid Suitable organic acids generally include, for example, aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes ot organic acids Specific examples of often suitable organic acids include acetate, trifluoroacetate, formate, propionate, succinate, glycolate, gluconate, digluconate, lactate, malate, tartaric acid, citrate, ascorbate, glucuronate, maleate, fumarate, pyruvate, aspartate, glutamate, benzoate, anthramlic acid, mesylate, stearate, salicylate, p-hydroxybenzoate, phenylacetate, mandelate, embonate (pamoate), ethanesulfonate, benzenesulfonate, pantothenate, 2-hydroxyethanesulfonate, sulfanilate, cyclohexylaminosulfonate, algenic acid, beta-hydroxybutyric acid, galactarate, galacturonate, adipate, alginate, bisulfate, butyrate, camphorate, camphorsulfonate, cyclopentanepropionate, dodecy Isulfate, glycoheptanoate, glycerophosphate, heptanoate, hexanoate, nicotmate, oxalate, palmoate, pectinate, 2-naphthalesulfonate, 3-phenylpropionate, picrate, pivalate, thiocyanate, tosylate, and undecanoate 100269] Pharmaceutically acceptable base addition sahs of the compounds of formula I include, for example, metallic salts and organic salts Preferred metallic salts include alkali metal (group la) salts, alkaline earth metal (group Ila) salts, and other physiol0gically acceptable metal salts Such salts may be made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc Preferred organic salts can be made from amines, such as tromethamine, diethylamine, N,N-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine), and procaine Basic nitr0gen-containing groups can be quaternized with agents such as lower alkyl (C1-C6) halides {e g, methyl, ethyl, propyl, and butyl chlorides, br0mldes, and iodides), dialkyl sulfates {e g, dimethyl, diethyl, dibutyl, and diamyl sulfates), long chain halides (e g, decyl, lauryl, mynstyl, and stearyl chlorides, br0mldes, and iodides), arylalkyi halides (e g, benzyl and phenethyl br0mldes), and others [00270] In some embodiments, the salt is sodium salt of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydr0-pyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00271] In some embodiments, the salt is monosodium salt ofN-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00272] In some embodiments, the salt is disodium salt of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydr0-pyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00273] In some embodiments, the salt is potassium salt of N-(6-(3-tert-butyl-5-(2,4-dlox0-3,4-dlhydr0-pyrlmldln-I(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamlde [00274] In some embodiments, the salt is monopotassium salt of N-(6-(3-tert-butyl-5-(2,4-diox0-3 4-dihydropynmidm-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00275] In some embodiments the salt is choline salt of N-(6-(3-tert-butyl-5-(2,4-dlox0-3,4-dlhydr0-pyrlmldln-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamlde [00276] In some embodiments, the salt is monocholine salt of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihvdropyrimidin-l(2H)-yl)-2-mcthoxyphenyl)naphthalen-2-yl)methanesulfonamide F Purity [00277] Compounds of formula I (and salts thereof) with any level of purity (including pure and substantially pure) are within the scope of Npplicants invention The term substantially pure m reference to a compoundsaltisomer, means that the preparationcomposition containing the compoundsaltisomer contains more than about 85%) by weight of the compoundsaltisomer, preferably more than about 90% by weight of the compoundsaltisomer, preferably more than about 95%) by weight of the compoundsaltisomer, preferably more than about 97%i by weight of the compoundsaltisomer, and preferably more than about 99% by weight of the compoundsaltisomer G Crystalline Forms of Some Specific Compounds and Salts oj The Invention Gl Crystalline Forms ofN-(6-(3-Tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 3) [00278] This invention also relates, in part, to crystalline forms of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-1 (2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 3), namely the solvate, hydrate, and solvent-free crystalline forms discussed below GIN IB-L0-2 3 Solvates [00279] This invention also relates, in part, to an ethanol solvate of compound IB-L0-2.3 [00280] In some embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 3±0 2, 9 7±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2, 19 2±0 2, 22 7±0 2, 26 9±0 2, and 29 4±0 2 degrees two theta (20) In some such embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 3±0 2, 9 7±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2, 19 2±0 2, 22 7±0 2, 26 9±0 2, and 29 4±0 2 degrees 26 In other such embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 3±0 2, 9 7±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2, 19 2±0 2, 22 7±0 2, 26 9±0 2, and 29 4±0 2 degrees 29 [00281] In some embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 3±0 2, 9 7±0 2, 10 0±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2,17 5±0 2, 19 2±0 2,19 4±0 2,22 7±0 2, 26 9±0 2, and 29 4±0 2 degrees 28 In some such embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 3±0 2, 9 7±0 2, 10 0±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2, 17 5±0 2, 19 2±0 2, 19 4±0 2, 22 7±0 2, 26 9±0 2, and 29 4-0 2 degrees 26 In other embodiments, the ethanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 3:tO 2 9 7±0 2, 10 0±0 2, 10 6±0 2, 13 6±0 2, 17 2±0 2, 17 5±0 2 19 2±0 2, 19 4±0 2, 22 7±0 2, 26 9±0 2, and 29 4±0 2 degrees 20 |00282]ln some embodiments, the ethanol solvate has an X-ray powder diffraction pattern substantially as shown in Figure 1 The 20 values for the peaks m Figure 1 (and their intensities) are as follows 8 25 (54), 9 67 (74), 9 92 (63), 10 59 (21) 13 64 (49), 17 25 (40), 17 51 (20), 19 19 (66), 19 43 (100), 22 75 (19), 26 92 (25), and 29 39 (18) [00283] This invention also relates, in part, to an acetonitnle solvate of compound IB-L0-2 3 [00284] In some embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, 10 5±0 2, 13 8±0 2, 17 2±0 2, 19 1±0 2, and 19 5±0 2 degrees 20 In some such embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, 10 5±0 2, 13 8±0 2, 17 2±0 2, 19 1±0 2, and 19 5±0 2 degrees 29 In other such embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, \ 0 5±0 2, 13 8±0 2, 17 2±0 2, 19 1±0 2, and 19 5±0 2 degrees 20 [00285] In some embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, 10 5±0 2, 13 8±0 2, 17 2±0 2, 17 7±0 2, 19 1±0 2, 19 5±0 2, 22 0±0 2, 22 8±0 2, and 27 2±0 2 degrees 29 In some such embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, 10 5±0 2, 13 8±0 2, 17 2±0 2, 17 7±0 2, 19 1±0 2, 19 5±0 2, 22 0±0 2, 22 8±0 2, and 27 2±0 2 degrees 20 In other such embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 3±0 2, 8 3±0 2, 9 7±0 2, 10 5±0 2, 13 8±0 2, 17 2±0 2, 17 7±0 2, 19 1±0 2, 19 5±0 2, 22 0±0 2, 22 8±0 2, and 27 2±0 2 degrees 20 [00286] In some embodiments, the acetonitnle solvate has an X-ray powder diffraction pattern substantially as shown in Figure 3 The 20 values for the peaks in Figure 3 (and their intensities) are as follows 5 27(14), 8 29(33), 9 72(100), 10 53(20), 13 77 (67), 17 25 (38), 17 69(17), 19 05(63), 19 47 (58), 22 05 (19), 22 75 (16), and 27 17 (21) [00287] This invention also relates, in part, to an ethyl acetate solvate of compound IB-L0-2.3 [00288] In some embodiments, the ethyl acetate solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 7 90 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 18 7±0 2, 38 5±0 2, and 44 7±0 2 degrees 29 In some such embodiments the ethyl acetate solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 7 9±0 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 18 7±0 2, 38 5±0 2, and 44 7t0 2 degrees 20 In other such embodiments, the ethyl acetate solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 7 9±0 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 18 7±0 2, 38 5±0 2, and 44 7±0 2 degrees 29 [00289] In some embodiments, the ethyl acetate solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 7 9±0 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 13 7±0 2, 17 4±0 2, 18 7±0 2, 21 7±0 2, 22 0±0 2, 28 2±0 2, 38 5:=0 2, and 44 7±G 2 degrees 29 In some such embodiments, the ethyl acetate solvate has an X-iay powder diffraction pattern comprising three or more peaks selected from the group consisting of 7 9 tO 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 13 7±0 2, 17 4±0 2, 18 7±0 2, 21 7±0 2, 22 0±0 2, 28 2±0 2, 38 5±0 2, and 44 7±0 2 degrees 29 In other such embodiments, the ethyl acetate solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 7 9±0 2, 9 3±0 2, 9 7±0 2, 10 6±0 2, 13 7±0 2, 17 4±0 2, 18 7±0 2, 21 7±0 2, 22 0±0 2, 28 2±0 2, 38 5±0 2, and 44 7±0 2 degrees 29 [00290] In some embodiments, the ethyl acetate has an X-ray powder diffraction pattern substantially as shown m Figure 4 The 26 values for the peaks in Figure 4 (and their intensities) are as follows 7 94 (24), 9 33 (26), 9 72 (13), 10 58 (23), 13 71 (19), 17 40 (28), 18 72 (44), 21 69 (8), 22 04 (10), 28 23 (8), 38 45 (100), and 44 66 (95) [00291] This invention also relates, in part, to a 2-propanol solvate of compound IB-L0-2 3 [00292] In some embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4±0 2, 21 6±0 2, and 22 5±0 2 degrees 29 In some such embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4±0 2, 21 6±0 2, and 22 5±0 2 degrees 29 In other such embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4J:0 2, 21 6±0 2, and 22 5±0 2 degrees 20 |00293]In some embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4±0 2, 21 6±0 2, 22 5±0 2, 23 8±0 2, 26 0±0 2, and 28 0±0 2 degrees 29 In some such embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4±0 2, 21 6±0 2, 22 5±0 2, 23 8±0 2, 26 0±0 2, and 28 0±0 2 degrees 20 In other such embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 16 3±0 2, 18 1±0 2, 18 6±0 2, 19 4±0 2 21 6±0 2, 22 5i:0 2, 23 8±0 2, 26 0±0 2, and 28 0±0 2 degrees 20 [00294] In some embodiments, the 2-propanol solvate has an X-ray powder diffraction pattern substantially as shown in Figure 5 The 20 values for the peaks in Figure 5 (and their intensities) are as follows 8 18(32) 9 26(100), 10 12(81), 16 28(93), 18 II (30) 18 59(63) 19 40(67), 21 57(60), 22 51 (31), 23 82 (29), 25 94 (24), and 28 05 (29) [00295] This invention also relates, in part, to a methanol solvate of compound IB-L0-2 3 [00296] In some embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 4±0 2, 9 7+0 2, 10 1±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, and 19 6±0 2 degrees 29 In some such embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 4±0 2, 9 7±0 2, 10 1±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, and 19 6±0 2 degrees 20 In other such embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 4±0 2, 9 7±0 2, 10 l±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, and 19 6±0 2 degrees 20 [00297] In some embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 4±0 2, 9 7±0 2, 10 1±0 2, 13 5±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, 19 6±0 2, and 27 1±0 2 degrees 20 In some such embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 4±0 2, 9 7±0 2, 10 1±0 2, 13 5±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, 19 6±0 2, and 27 1±0 2 degrees 29 In other such embodiments, the methanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 4±0 2, 9 7±0 2, 10 I±0 2, 13 5±0 2, 13 8±0 2, 17 4±0 2, 19 3±0 2, 19 6±0 2, and 27 1±0 2 degrees 20 [00298] In some embodiments, the methanol solvate has an X-ray powder diffraction pattern substantially as shown in Figure 6 The 20 values for the peaks in Figure 6 (and their intensities) are as follows 8 36 (48), 9 74 (65), 10 05 (74), 13 55 (24), 13 79 (69), 17 40 (32), 19 30 (80), 19 58 (100), and 27 08 (24) [00299] This invention also relates, in part, to a 1-propanol solvate of compound IB-L0-2_3 [00300] In some embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 15 7±0 2, 16 2 ±0 2, 18 4±0 2, 19 3±0 2,21 6±0 2, and 22 8±0 2 degrees 20 In some such embodiments, the 1-propano! solvate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 2±0 2,9 3±0 2,10 1±0 2,15 7±0 2, 16 2 ±0 2, 18 4±0 2, 19 3±0 2, 21 6±0 2, and 22 8±0 2 degrees 26 In other such embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 15 7±0 2, 16 2 ±0 2 18 4±0 2, 19 3±0 2, 21 6±0 2, and 22 8±0 2 degrees 26 [00301] In some embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 2i-0 2, 9 3±0 2, 10 1±0 2, 10 5±0 2, 15 7±0 2, 16 2 ±0 2, 18 4±0 2, 18 6±0 2, 19 3±0 2, 2! 0±0 2, 21 6±0 2 and 22 8±0 2 degrees 29 In some such embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern compiising three or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2, 10 5±0 2, 15 7±0 2. 16 2 ±0 2, 18 4±0 2, 18 6±0 2, 19 3±0 2, 21 0±0 2, 21 6±0 2, and 22 8±0 2 degrees 20 In other such embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 2±0 2, 9 3±0 2, 10 1±0 2. 10 5±0 2, 15 7±0 2, 16 2 ±0 2, 18 4±0 2, 18 6±0 2, 19 3±0 2, 21 0±0 2, 21 6±0 2, and 22 8±0 2 degrees 26 [00302] In some embodiments, the 1-propanol solvate has an X-ray powder diffraction pattern substantially as shown in Figure 7 The 26 values for the peaks in Figure 7 (and their intensities) are as follows 8 15 (27), 9 26 (87), 10 08 (84), 10 47 (62), 15 73 (40), 16 24 (100), 18 37(41), 18 59(49), 19 33 (50), 20 97 (28), 21 65 (71), and 22 81 (44) [00303] This invention also relates, in part, to a process for preparing the above solvates by suspending compound IB-L0-2 3 m the corresponding solvent GIB Solvent Free IB-L0-2 3 [00304] This invention also relates, m part, to a solvent free crystalline form of compound IB-L0-2 3 [00305] In some embodiments, the solvent free compound IB-L0-2 3 has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 16 2±0 2, and 18 3±0 2 degrees two theta (26) In some such embodiments, the solvent free compound IB-L0-2.3 has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 16 2±0 2, and 18 3±0 2 degrees 26 In other such embodiments, the solvent free compound IB-L0-2 3 has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 16 2±0 2, and 18 3±O2degrees20 [003061 In some embodiments, the solvent free compound IB-L0-2.3 has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 10 1±0 2, 14 9±0 2, 16 2±0 2, 18 3±0 2,19 8±0 2, and 26 5±6 2 degrees 26 In some such embodiments, the solvent free compound IB-L0-2 3 has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 10 1±0 2, 14 9±0 2, 16 2±0 2, 18 3±0 2, 19 8±0 2, and 26 5±0 2 degrees 26 In other such embodiments, the solvent free compound IB- L0-2 3 has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 6 20 2, 7 9±0 2, 9 90 2, 10 1 ±0 2, 14 9±0 2, 16 2±0 2, 18 3±0 2, 19 8±0 2 and 26 5±0 2 degrees 26 In yet other such embodiments, the solvent free compound IB-L0-2 3 has an X-ray powder diffraction pattern comprising eight or more peaks selected from the group consisting of 6 2±0 2, 7 9±0 2, 9 9±0 2, 10 1±0 2, 14 9±0 2, 16 2±0 2 18 3±0 2, 19 8±0 2, and 26 5±0 2 degrees 26 [00307] In some embodiments, the solvent free compound IB-L0-2 3 has an X-ray powder diffraction pattern substantially as shown m Figure 8 The 26 values for the peaks in Figure 8 (and their intensities) are as follows 6 20 (36), 7 85 (66), 9 89 (61), 10 12(75), 14 87(27), 16 19(89), 18 32(100), 19 82(77), and 26 53 (34) [00308] This invention also relates, in part, to a process for preparing the solvent free crystalline form of compound IB-L0-2 3 by desolvatmg one of IB-L0-2 3 solvates discussed above N solvate can be desolvated by heating the solvate solid for about 10min at -125 C GIC IB-L0-2 3 Hydrate [00309] This invention also relates, m part, to a hydrate of compound IB-L0-2 3 [00310] In some embodiments, the hydrate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6 4±0 2, 12 9±0 2,17 9±0 2, and 18 9±0 2 degrees 20 In some such embodiments, the hydrate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 6 4±0 2, 12 9±0 2, 17 9±0 2, and 18 9±0 2 degrees 20 [00311] In some embodiments, the hydrate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6 4±0 2, 12 9±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, and 24 4±0 2 degrees 20 In some such embodiments, the hydrate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 6 4±0 2, 12 9±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, and 24 4±0 2 degrees 20 In other such embodiments, the hydrate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 6 4±0 2, 12 9±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, and 24 4±0 2 degrees 26 [00312] In some embodiments, the hydrate has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6 4±0 2, 12 7±0 2, 12 9±0 2, 14 1±0 2, 15 7±0 2, 17 2±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, 21 2±0 2, 24 4±0 2, and 25 0±0 2 degrees 26 In some such embodiments, the hydrate has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 6 4±0 2, 12 7±0 2, 12 9±0 2, 14 1±0 2, 15 7±0 2, 17 2±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, 21 2±0 2, 24 4±0 2, and 25 0±0 2 degrees 29 In other such embodiments, the hydrate has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 6 4±0 2, 12 7±0 2, 12 9±0 2, 14 1±0 2, 15 7±0 2, 17 2±0 2, 17 5±0 2, 17 9±0 2, 18 9±0 2, 21 2±0 2, 24 4±0 2, and 25 0±0 2 degrees 28 [00313] In some embodiments, the hydrate has an X-ray powder diffraction pattern substantially as shown in Figure 9 The 29 values for the peaks in Figure 9 (and their intensities) are ab follows 6 42 (60), 12 71 (33), 12 89(58), 14 05(17), 15 68(18), 17 22(44), 17 53(100), 17 86(51), 18 87(77), 21 25 (17), 24 35 (28), and 24 95 (20) [00314] This invention also relates, in part, to d process for preparing the hydrate by suspending the above-described solvent free crystalline compound in water The hydrate was prepared by suspending 300mg ot the solvent free crystalline compound in 2ml of water at 45C for four days G2 Crystalline Forms ofN-(6-(3-Tert-butyl-5-(2,4-diox0-i,4-dihydropynmidm-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methcmesulfonamide, Monosodium Salt [00315]This invention also relates, in part, to crystalline forms of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, monosodium salt, namely the pattern N, pattern B, and pattern C crystalline forms discussed below [00316]This invention relates, in part, to a pattern N crystalline monosodium salt [00317] In some embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 18 6±0 2, 22 8±0 2, and 23 9±0 2 degrees 29 In some such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 18 6±0 2, 22 8±0 2, and 23 9±0 2 degrees 20 In other such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 18 6±0 2, 22 8±0 2, and 23 9±0 2 degrees 20 [00318] In some embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2,12 0±0 2, 15 6±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, and 23 9±0 2 degrees 20 In some such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6i0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, and 23 9±0 2 degrees 29 In other such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, and 23 9±0 2 degrees 20 [00319] In some embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 16 0±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, 23 9±0 2, and 28 3±0 2 degrees 29 In some such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0±0 2, 15 6±0 2, 16 0±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, 23 9±0 2, and 28 3±0 2 degrees 20 In other such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 4 6±0 2, 10 4±0 2, 12 0+0 2, 15 6±0 2 16 0±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, 23 9±0 2, and 28 3i0 2 degrees 26 In other such embodiments, the pattern N monosodium salt has an X- ray powder diffraction pattern comprising eight or more peaks selected from the group consisting of 4 6±0 2 10 4±0 2 12 0±0 2, 15 6±0 2, 16 0±0 2, 18 6±0 2, 22 8±0 2, 23 3±0 2, 23 9±0 2, and 28 3±0 2 degrees 26 [00320] In some embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern substantially as shown in Figure 10 The 26 values tor the peaks in Figure 10 (and their intensities) are as follows 4 64 (62), 10 41 (38), 12 04 (38), 15 62 (44), 15 99 (44), 18 63 (49) 22 77 (60), 23 29 (40), 23 93(100), and 28 31 (56) [00321] This invention also relates, in part, to a process for preparing the pattern N monosodium salt The pattern N monosodium salt was prepared by adding IM aqueous NaOH (0 548ml) to compound IB- L0-2.3 (225 72mg), seeding the resulting suspension with crystalline N-(6-(3-tcrt-butyl-5-(2,4-diox0-3,4- dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, disodium salt (prepared as discussed below), and equilibrating the resulting suspension at ambient conditions The pattern N monosodium salt was formed on the following day through a solution-mediated process The stoichiometry of the salt was presumed to be 1 1 based on the crystallization procedure This invention also relates, in part, to a pattern B crystalline monosodium salt [00323] Tn some embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2,21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 20 In some such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 20 In other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 20 [00324] In some embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 I±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2, and 31 8±0 2 degrees 29 In some such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2, and 31 8±0 2 degrees 29 In other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consistmg of 5 4±0 2 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0=0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2, and 31 8±0 2 degrees 20 In other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising eight or more peaks selected from the group consisting of5 4±0 2 10 8±0 2, I4 4±0 2, 16 3±0 2, 17 0i0 2, 18 8±0 2, 19 20 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2, and 31 8±0 2 degrees 29 [00325] In some embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2 and 31 8±0 2 degrees 26 In some such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising two or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 29 1±0 2, and 31 8±0 2 degrees 29 In other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising two or more peaks selected from the group consistmg of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, and 31 8±0 2 degrees 20 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, and 31 8±0 2 degrees 26 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 29 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 19 2±0 2, 21 6±0 2, 22 l±0 2, and 23 7±0 2 degrees 26 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 29 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 20 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 4±0 2, 10 80 2, 16 3±0 2, 22 1±0 2, and 23 7±0 2 degrees 20 [00326] In some embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, and 16 3±0 2 degrees 20 In some such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern compnsmg peaks at 5 4±0 2, 10 8±0 2, 16 3±0 2, and 22 1±0 2 degrees 26 In other such embodiments, the pattern B monosodium salt has an X- ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 16 3±0 2, 22 1±0 2, and 23 7±0 2 degrees 26 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern compnsmg peaks at 5 4±0 2, 10 8±0 2, 14 4:0 2, 16 3±0 2, 17 0±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 26 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 21 6±0 2, 22 I±0 2, and 23 7±0 2 degrees 29 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 19 2±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 29 In yet other such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 21 6±0 2, 22 1±0 2, and 23 7±0 2 degrees 29 In further such embodiments the pattern B monosodium salt has an X-ray powder diffraction pattern compnsmg peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2,17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, and 31 8±0 2 degrees 20 In yet further such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, and 31 8±0 2 degrees 29 In yet further such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2, 19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 29 1±0 2, and 31 8±0 2 degrees 20 In yet further such embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern comprising peaks at 5 4±0 2, 10 8±0 2, 14 4±0 2, 16 3±0 2, 17 0±0 2, 18 8±0 2,19 2±0 2, 19 6±0 2, 21 6±0 2, 22 1±0 2, 23 7±0 2, 28 8±0 2, 29 1±0 2, and 31 8±0 2 degrees 20 [00327] In some embodiments, the pattern B monosodium salt has an X-ray powder diffraction pattern substantially as shown in Figure 12 The 20 values for the peaks in Figure 12 (and their mtensittes) are as follows 5 36(100), 10 75(42), 14 43(20), 16 34 (60), 17 00 (25), 18 83 (18), 19 24 (18), 19 66 (12), 21 64 (29), 22 12 (41), 23 73 (32), 28 83 (9), 29 10 (9), and 31 78 (10) [00328J This invention also relates, in part, to a process for preparing the pattern B monosodium salt The pattern B monosodium salt can prepared by suspending the pattern N monosodium salt (for example, ~ 30mg) in various organic solvents (e g , ~ 125ul acetonitrile, ethanol, 1-propanol, or 2-propanol) at room temperature The pattern B monosodium salt was also prepared by seeding a solution with pattern B monosodium salt Compound IB-L0-2 3 (12 5g) was dissolved in DMSO (37 5ml) at ~68°C 1 04g NaOH dissolved in 6 3ml of water, 6 3ml 2-propanol, and 12 5ml 35 2 1 vv 2-propanolwater was added The solution was seeded with 125mg of pattern B seeds slurried in 12 5ml of 35 2 1 vv 2-propanolwater, and the crystallization slurry was incubated at ~68C for ~1 5h 175ml 35 2 1 vv 2-propanolwater at -68 was added over ~7h, and the crystallization slurry was cooled to ~0V over no less than 7h The crystals were isolated by filtration and analyzed by PXRD The crystals v\ere then dried at -SOC under vacuum (approximately 3 inches of mercury) The dried crystals were analyzed by PXRD, which showed no change m comparison to the pre-drying sample The stoichiometry of the pattern B monosodium salt was confirmed by ion chromat0graphy [00329]This invention also relates, in part, to a pattern C crystalline monosodium salt [00330] In some embodiments, the pattern C monosodium sah has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 0±0 2, 12 0±0 2 17 5±0 2, 18 8±0 2, and 22 7±0 2 degrees 20 In some such embodiments, the pattern C monosodium salt has an X- ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 0±0 2, 12 0±0 2, 17 5±0 2, 18 8±0 2, and 22 7±0 2 degrees 26 [00331] In some embodiments, the pattern C monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 0±0 2, 12 0±0 2, 17 5±0 2, 17 8±0 2, 18 8±0 2, and 22 7±0 2 degrees 29 In some such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 0±0 2, 12 0±0 2 17 5±0 2, 17 8±0 2, 18 8±0 2, and 22 7±0 2 degrees 20 In other such embodiments, the pattern N monosodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 0±0 2, 12 0±0 2, 17 5±0 2, 17 8±0 2, 18 8±0 2, and 22 7±0 2 degrees 29 [00332] In some embodiments, the pattern C monosodium salt has an X-ray powder diffraction pattern substantially as shown m Figure 14 The 29 values for the peaks in Figure 14 (and their intensities) are as follows 4 97 (100), 12 03 (24), 17 55 (32), 17 80 (77), 18 79 (23), and 22 74 (33) [00333] This invention also relates, m part, to a process for preparing the pattern C monosodium salt The pattern C monosodium salt was prepared as follows Pattern B monosodium salt (100mg) was dissolved in 400ul DMSO and 2ml 12 1 vv 2-propanolH20 at 70°C Pattern B monosodium salt seed crystals were added to the solution, and the solution was then cooled to ambient temperature over 20min Filtration yielded crystals of the pattern C monosodium salt G3 Crystalline Form ofN-(6-(3-Tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidm-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, Disodium Salt [00334] This invention also relates, m part, to a crystalline form of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyI)naphthalen-2-yl)methanesuIfonamide, disodium salt [00335] In some embodiments, the disodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4 8±0 2,9 6±0 2, 10 5±0 2, 13 0±0 2, 14 6±0 2, 15 4±0 2, 16 8 ±0 2, and 23 0±0 2 degrees 29 In some such embodiments, the disodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 4 8±0 2, 9 6±0 2, 10 5±0 2 13 0±0 2, 14 6±0 2, 15 4±0 2, 16 8 ±0 2 and 23 0±0 2 degrees 26 In other such embodiments, the disodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 4 8±0 2, 9 6±0 2, 10 5±0 2, 13 0±0 2 14 6±0 2, 15 4±0 2, 16 8 ±0 2, and 23 0±0 2 degrees 20 [00336] In some embodiments, the disodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4 8±0 2, 9 6±0 2, 10 5±0 2, 13 0±0 2, 14 6±0 2, 15 4±0 2, 16 8 ±0 2, 22 7±0 2, 23 0±0 2, and 23 3±0 2 degrees 26 In some such embodiments, the disodium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consistmg of 4 8±0 2, 9 6±0 2, 10 5±0 2, 13 0±0 2, 14 6±0 2, 15 4±0 2, 16 8 ±0 2, 22 7±0 2, 23 0±0 2, and 23 3±0 2 degrees 29 In other such embodiments, the disodium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 4 8±0 2, 9 6±0 2, 10 5±0 2, 13 0±0 2, 14 6±0 2, 15 4±0 2, 16 8 ±0 2, 22 7±0 2, 23 0±0 2, and 23 3±0 2 degrees 29 [00337] In some embodiments, the disodium salt has an X-ray powder diffraction pattern substantially as shown in Figure 15 The 20 values for the peaks in Figure 15 (and their intensities) are as follows 4 80 (100), 9 59 (10), 10 51 (13), 12 98 (11), 14 56 (8), 15 38 (12), 16 84 (6), 22 68 (10), 23 04 (6), and 23 33 (4) [00338] This invention also relates, in part, to a process for preparing the disodium salt The disodium salt was prepared by suspending compound IB-L0-2 3 (52 83mg) m IM aqueous NaOH (1 1ml) (the molar ratio compound NaOH was I 10) The solution was heated to 36C, and the solid dissolved completely to yield a clear solution The solution was naturally cooled to ambient temperature, and the salt crystallized in 24h Nlternatively, the disodium salt was prepared by suspending compound IB-L0-2 3 (5Img) in EtOH (Iml) NaOH in 1 2ml of 5 1 vv EtOHHjO (2 1 molar equivalent) was added The reaction mixture was concentrated and 2ml acetonitrile was added to induce crystallization The stoichiometry of this solid was determined by ion chromat0graphy G4 Crystalline Form ofN-(6-(3-Tert-butyl-5-(2,4-diox0-3,4-dihydropynmidm-I(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, Monopotassium Salt [00339]This invention also relates, m part, to a crystalline form of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-1 (2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, monopotassium salt [00340] In some embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2, 11 3±0 2, 13 3±0 2, 16 9±0 2, 18 1±0 2, 19 1±0 2, 20 0±0 2, 21 1±0 2, 23 5±0 2, 24 8±0 2, and 25 7±0 2 degrees 20 In some such embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2, 11 3±0 2, 13 3±0 2, 16 9±0 2, 18 1±0 2, 19 1±0 2, 20 0±0 2, 21 1±0 2, 23 5±0 2, 24 8±0 2 and 25 7±0 2 degrees 26 In other such embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2 11 3±0 2, 13 3±0 2, 16 9±0 2, 18 1±0 2, 19 1±0 2 20 0±0 2, 21 1±0 2, 23 5±0 2, 24 8±0 2, and 25 7±0 2degrees 28 [00341] In some embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2, 11 3±0 2, 13 3±0 2, 16 9±0 2, 18 1±0 2, 19 1±0 2, 20 0±0 2, 21 1±0 2, 21 5±0 2, 23 5±0 2, 24 8±0 2, and 25 7±0 2 degrees 29 In some such embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2, 11 3±0 2, 13 3±0 2,16 9±0 2, 18 1±0 2, 19 1±0 2, 20 0±0 2, 21 1±0 2, 21 5±0 2, 23 5±0 2, 24 8±0 2, and 25 7±0 2 degrees 29 In other such embodiments, the monopotassium salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 5 0±0 2, 9 9±0 2, 11 3±0 2, 13 3±0 2 16 9±0 2, 18 1±0 2, 19 1±0 2, 20 0±0 2, 21 1±0 2, 21 5±0 2, 23 5±0 2, 24 8±0 2, and 25 7±0 2degrees 29 [00342] In some embodiments, the monopotassium salt has an X-ray powder diffraction pattern substantially as shown in Figure 17 The 29 values for the peaks in Figure 17 (and their intensities) are as follows 4 97(100), 9 94(7), 11 33(15), 1328(7), 16 91 (5), 18 13(7), 19 14 (4), 20 00 (4), 21 13(4), 21 45 (4), 23 54 (4), 24 84 (3), and 25 67 (6) [00343] This invention also relates, m part, to a process for preparing the monopotassium salt The monopotassium salt was prepared in aqueous medium 0 366ml of IM aqueous KOH was added to 150 56mg of compound IB-L0-2 3 (molar ratio 1 1 2) The resulting suspension was equilibrated at ambient conditions The monopotassium salt was formed on the following day through a solution-mediated process Nlternatively, the monopotassium salt was prepared by suspending compound IB-L0-2 3 (300mg) in 3ml acetonitnle KOH in 1 3mL of H2O (2 1 molar equivalent) was added Ndditional 1ml H2O was added to dissolve all solids Nfterwards, 12ml acetonitnle was added to induce crystallization The stoichiometry of the salt was confirmed by ion chromat0graph G5 Crystalline Forms ofN-(6-(3-Tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, Monocholine Salt [00344]This invention also relates, in part, to crystalline forms of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-1 (2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, monocholine salt, namely the pattern N and pattern B crystalline forms discussed below [00345JThis invention relates, m part, to a pattern N crystalline monocholine salt [00346] In some embodiments, the pattern N monocholine salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10 9±0 2, 12 1±0 2, 13 4±0 2, 15 5±0 2, 17 0±0 2, 17 8±0 2, 18 3i0 2, 19 5±0 2, and21 9±0 2 degrees 29 In some such embodiments, the pattern N monocholine salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 10 9±0 2, 12 1±0 2, 13 4±0 2, 15 5±0 2, 17 0±0 2, 17 8iO 2, 18 3±0 2, 19 5±0 2 and 21 9±0 2 degrees 29 In other such embodiments, the pattern N monocholine salt has an X-ray powder diffraction pattern comprismg five or more peaks selected from the group consisting ofl0 9±0 2, 12 1±0 2, 13 4±0 2, 15 5i0 2, 17 0±0 2, 17 8±0 2, 18 3±0 2, 19 5±0 2, and 21 9±0 2 degrees 20 {00347) In some embodiments, the pattern N monochohne salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10 9±0 2, 12 1±0 2, 13 0±0 2, 13 4±0 2, 13 6±0 2, 15 5±0 2, 17 0±0 2, 17 8±0 2, 18 3±0 2, 19 5±0 2, 19 7±0 2, and21 9±0 2 degrees 29 In some such embodiments, the pattern N monochohne salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of degrees 29 In other such embodiments, the pattern N monochohne salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of degrees 20 [00348] In some embodiments, the pattern N monochohne salt has an X-ray powder diffraction pattern substantially as shown in Figure 19 The 29 values for the peaks in Figure 19 (and their intensities) are as follows 10 94(42), 12 06(20), 12 96(26), 13 42(64), 13 64(27), 15 51(18), 16 98(78), 17 81 (26), 18 32 (100), 19 49 (48), 19 70 (33), and 21 91 (22) [00349] This invention also relates, in part, to a process for preparing the pattern N monocholine salt It was prepared in a solvent mixture of tetrahydrofuran (THF) and methanol Compound IB-L0-2 3 (56 79mg) was dissolved in THF at 60°C, 40 Olmg of choline hydroxide solution (45vv1% m methanol) was added resulting in a molar ratio of 1 1 2 The crystals formed upon natural cooling to ambient temperature [00350] This invention also relates, in part, to a pattern B crystalline monocholine salt [00351] In some embodiments, the pattern B monochohne salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 0±0 2, 9 4±0 2, 11 0±0 2, 13 0±0 2, 13 7±0 2, 15 9±0 2, 17 0±0 2, 18 3±0 2, 18 9±0 2, 19 8±0 2, and 22 1±0 2 degrees 2G In some such embodiments, the pattern B monochohne salt has an X-ray powder diffraction pattern comprising three or more peaks selected firom the group consisting of 8 0±0 2, 9 4±0 2, 11 0±0 2, 13 0±0 2, 13 7±0 2, 15 9±0 2, 17 0±0 2, 18 3±0 2, 18 9±0 2, 19 8±0 2, and 22 1±0 2 degrees 20 In other such embodiments, the pattern B monochohne salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 0±0 2, 9 4±0 2, 11 0±0 2, 13 0±0 2, 13 7±0 2, 15 9±0 2, 17 0±0 2, 18 3±0 2, 18 9±0 2, 19 8±0 2, and 22 1±0 2 degrees 20 [00352] In some embodiments, the pattern B monocholine salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 0±0 2, 9 4±0 2, 11 0±9 2, 13 0±0 2 13 3±9 2, 13 7±9 2, 15 9±9 2, 17 9±0 2, 17 4±9 2 18 3±0 2, 18 9±0 2, 19 8±9 2,21 8±9 2, and 22 1±0 2 degrees 29 In some such embodiments, the pattern B monocholine salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 0±0 2, 9 4±0 2, 11 0+0 2, 13 0±0 2, 13 3±0 2, 13 7±0 2, 15 9±0 2, 17 0±0 2, 17 4±0 2, 18 3±0 2, 18 9±0 2, 19 8:t:0 2,21 8±0 2,and 22 1±0 2 degrees 20 In other such embodiments, the pattern B monocholine salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 0±0 2, 9 4±0 2, 11 0±0 2, 13 0±0 2, n 3±0 2, 13 7±0 2, 159±0 2, 170±0 2, 174±0 2, 183±0 2, 189±0 2, 198±0 2, 21 8±0 2, and 22 1±0 2 degrees 29 [00353] In some embodiments, the pattern B monocholine salt has an X-ray powder diffraction pattern substantially as shown in Figure 21 The 29 values for the peaks in Figure 21 (and their intensities) are as follows 7 96 (41), 9 38 (34), 10 96 (24), 12 98 (76), 13 34 (33), 13 72 (37), 15 90 (100), 17 03 (60), 17 42(37), 18 30(31), 18 85(93), 19 82 (90), 21 76 (38), and 22 06 (46) [00354] This invention also relates, in part, to a process for preparing the pattern B monocholme salt It was prepared by suspending amorphous choline salt in ethyl acetate for seven days G6 Crystalline Form ofN-(6-(3-Tert-butyl-5-(2,4-diox0-3,4-dihydropynmidm-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide, Dicholine Salt [00355] This invention also relates, m part, to a crystalline form of N-(6-(3-tert-butyl-5-(2,4-dIox0-3,4-dlhydropyrImldln-l(2H)-yl)-2-methoxyphenyI)naphthalen-2-yl)methanesulfonamlde, dicholine salt [00356] In some embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9±0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, and 21 9±0 2 degrees 29 In some such embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9±0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, and 21 9±0 2 degrees 29 In other such embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9±0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, and 21 9±0 2 degrees 29 [00357] In some embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9t0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, 21 9±0 2, and 22 1±0 2 degrees 29 In some such embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9±0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, 21 9±0 2, and 22 1±0 2 degrees 20 In other such embodiments, the dicholine salt has an X-ray powder diffraction pattern comprising five or more peaks selected from the group consisting of 8 6±0 2, 11 0±0 2, 12 9±0 2, 17 0±0 2, 17 5±0 2, 18 9±0 2, 19 8±0 2, 21 9±0 2, and 22 1±0 2 degrees 29 [00358]In some embodiments, the dichohne salt has an X-ray powder diffraction pattern substantially as shown in Figure 23 The 29 values for the peaks in Figure 23 (and their intensities) are as follows 8 62 (28), 10 98 (29), 12 93 (50), 15 88 (100), 17 03 (42), 17 47 (29), 18 88 (66), 19 82 (57), 21 89 (42), 2 07 (41) 100359]This invention also relates, in part, to a process for preparing the dichohne salt It was prepared by suspending compound IB-L0-2 3 (200mg) in 0 75ml MeOH Choline hydroxide in MeOH (210ml, 45wt%, 2 10 molar equivalent) was added The reaction mixture was concentrated, and 4ml acetonitnle and 6ml isopropyl acetate were added The reaction mixture was then seeded with trace amount ol the compound IB-L0-2 3 monopotassium salt seed crystals (discussed above) The reaction mixture started to crystallize shortly after Fhe stoichiometry of the salt was determined by solution H NMR H Compositions [00360] This invention also is directed, in part, to compositions comprising one or more compounds andor salts of the invention (including the crystalline compounds and salts discussed in section G above) In some embodiments, the compositions comprise one or more substantially phase pure crystalline forms (compoundssaltssolvateshydrates) discussed in section G above The compositions can be pharmaceutical compositions [00361] In some embodiments, the compositions further comprise one or more additional therapeutic agents Such therapeutic agents can, but need not be, additional HCV inhibitors [00362] The preferred composition depends on the method of administration, and typically comprises one or more conventional pharmaceutically acceptable carriers, adjuvants, andor vehicles (t0gether referred to as excipients) Formulation of drugs is generally discussed in, for example, FFoover, J , Remingtons Pharmaceutical Sciences (Mack Publishing Co , 1975) and Nnsels Pharmaceutical Dosage Forms and Drug Delivery Systems (Lippincott Williams & Wilkins, 2005) [00363] Solid dosage forms for oral administration include, for example, capsules, tablets, pills, powders, and granules In such solid dosage forms, the compounds or salts are ordinarily combined with one or more excipients If administered per os, the compounds or salts can be mixed with, for example, lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, andor polyvinyl alcohol, and then tableted or encapsulated for convenient administration Such capsules or tablets can contain a controlled-release formulation, as can be provided m, for example, a dispersion of the compound or salt m hydroxypropylmethyl cellulose In the case of capsules, tablets, and pills, the dosage forms also can comprise buffering agents, such as sodium citrate, or magnesium or calcmm carbonate or bicarbonate Tablets and pills additionally can be prepared with enteric coatings [00364] Liquid dosage forms for oral administration include, for example, pharmaceutically acceptable emulsions (including both oil-in-vvater and water-in-oil emulsions), solutions (including both aqueous and non-aqueous solutions), suspensions (including both aqueous and non-aqueous suspensions), syrups, and elixirs containing inert diluents commonl\ used in the art (e g, water) Such compositions also can comprise, for example, wetting, emulsifying, suspending, flavoring (e g, sweetening), andor perfuming agents [00365]Parenteral administration includes subcutaneous injections, intravenous injections, intramuscular injections, intrastemal injections, and infusion Injectable preparations (e g, sterile injectable aqueous or oleaginous suspensions) can be formulated according to the known art using suitable dispersing, wetting agents, andor suspending agents Ncceptable vehicles and solvents include, for example, water, 1,3- butanediol, Ringers solution, isotonic sodium chloride solution, bland fixed oils (e g, synthetic mon0- or diglycendes), fatty acids {e g, oleic acid), dimethyl acetamide, surfactants (e g, ionic and non-ionic detergents), andor polyethylene glycols [00366] Formulations for parenteral administration may, for example, be prepared from sterile powders or granules having one or more of the excipients mentioned for use in the formulations for oral administration N compound or salt of the invention can be dissolved in water, polyethylene glycol, propylene glycol, ethanol, com oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, andor various buffers The pH may be adjusted, if necessary, with a suitable acid, base, or buffer [00367] Suppositories for rectal administration can be prepared by, for example, mixing a compound or salt of the invention with a suitable nonimtating excipient that is solid at ordinary temperatures, but liquid at the rectal temperature, and will therefore melt m the rectum to release the drug Suitable excipients include, for example, cocoa butter, synthetic mon0-, di-, or triglycerides, fatty acids, andor polyethylene glycols [00368] Topical administration includes the use of transdermal administration, such as transdermal patches or iontophoresis devices [00369[ Other excipients and modes of administration known in the pharmaceutical art also may be used [00370] The preferred total daily dose of the compound or salt (administered in single or divided doses) is typically from about 0 001 to about 100mgkg, more preferably from about 0 001 to about 30mgkg, and even more preferably from about 0 01 to about 10mgkg (i e ,mg of the compound or salt per kg body weight) Dosage unit compositions can contain such amounts or submultiples thereof to make up the daily dose In many instances, the administration of the compound or salt will be repeated a plurality of times Multiple doses per day typically may be used to increase the total daily dose, if desired [00371] Factors affecting the preferred dosage regimen include the type, age, weight, sex, diet, and condition of the patient, the severity of the pathol0gical condition, the severity of the pathol0gical condition, the route of administration, pharmacol0gical considerations, such as the activity, efficacy, pharmacokinetic, and toxicol0gy profiles of the particular compound or salt used, whether a drug deliver} system is utilized, and whether the compound or salt is administered as part of a drug combination Thus, the dosage regimen actually employed can vary widely, and therefore, can derive from the preferred dosage regimen set forth above Kits [00372] This invention also is directed, in part, to a kit comprising one or more compounds andor salts of the in mvention The kit can optionally contain one or more additional therapeutic agents andor mstructions for, for example, using the kit Methods of Use [00373] This invention also is directed, in part, to a method for inhibiting replication of an RNN virus The method comprises exposing the virus to one or more compounds andor salts of this invention In some embodiments, replication of the RNN virus is inhibited in vitro In other embodiments, replication of the RNN virus is inhibited in vivo In some embodiments, the RNN virus whose replication is being inhibited is a single-stranded, positive sense RNN virus In some such embodiments, the RNN virus whose replication is being inhibited is a virus from the Flaviviridae family In some such embodiments, the RNN virus whose replication is being inhibited is HCV [00374] This invention also is directed, in part, to a method for inhibiting HCV RNN polymerase The method comprises exposing the polymerase with one or more compounds andor salts of this invention In some embodiments, HCV RNN polymerase activity is inhibited m vitro In other embodiments, HCV RNN polymerase activity is inhibited in vivo J00375]The term inhibiting means reducing the level of RNN virus replicationHCV polymerase activity either in vitro or in vivo For example, if a compoundsalt of the invention reduces the level of RNN virus replication by at least about 10% compared to the level of RNN virus replication before the virus was exposed to the compoundsalt, then the compoundsalt inhibits RNN virus replication In some embodiments, the compoundsalt can inhibit RNN virus replication by at least about 20%, at least about 30%, at least about 40%y, at least about 50%), at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% [00376] This invention also is directed, in part, to a method for treating a disease that can be treated by inhibiting HCV RNN polymerase Thus, this invention also is directed, in part, to a method for treating hepatitis C in an animal in need of such treatment These methods comprise administering to the animal one or more compounds andor salts of the invention, and, optionally, one or more additional therapeutic agents In some embodiments, a therapeutically effective amount of the compound(s) andor sa]t(s) is administered to the animal Treating means ameliorating, suppressing, eradicating, preventing, reducing the risk of, andor delaying the onset of the disease being treated Npplicants specifically intend that the term treating encompass administration of the compounds andor salts of the invention to an HCV-negative patient that is a candidate for an organ transplant The methods of treatment are particularly suitable for use with humans, but may be used with other animals, particularly mammals N therapeutically-effective amount or effective amount is an amount that will achieve the goal of treating the targeted condition [00377] In some embodiments, the methods comprise combination therapy, wherein the compound(s) andor salt(s) of the invention isare c0-administered with a second (or even a third, fourth, etc ) compound, such as, for example, another therapeutic agent used to treat hepatitis C (e g, interferon or interferonribavirin combination, or an HCV inhibitor such as, for example, an HCV polymerase inhibitr or an HCV protease inhibitor) The compound(s) andor salt(s) of this invention can also be coadministered with therapeutic agents other than therapeutic agents used to treat hepatitis C(e g, anti-HIV agents) In these c0-admmistration embodiments, the compound(s) andor salt(s) of the invention and the second, etc therapeutic agent(s) may be administered in a substantially simultaneous manner (e g, or within about 5 minutes of each other), in a sequential manner, or both It is contemplated that such combination therapies may include administering one therapeutic agent multiple times between the administrations of the other The time period between the administration of each agent may range from a few seconds (or less) to several hours or days, and will depend on, for example, the properties of each composition and active ingredient (e g, potency, solubility, bioavailability, half-life, and kinetic profile), as well as the condition of the patient The compound(s) andor salt(s) of this invention and the second, etc therapeutic agent may also be administered in a single formulation [00378] This invention also is directed, in part, to a use of one or more compounds andor salts of the invention, and, optionally one or more additional therapeutic agents to prepare a medicament In some embodiments, the medicament is for c0-administration with one or more additional therapeutic agents [00379] In some embodiments, the medicament is for inhibiting replication of an RNN virus [00380] In some embodiments, the medicament is for treating hepatitis C [00381] This invention also is directed, m part, to one or more compounds andor salts of the invention, and, optionally one or more additional therapeutic agents, for use as a medicament In some embodiments, the medicament is for inhibiting replication of an RNN virus In other embodiments, the medicament is for treating hepatitis C K Inlet mediate Compounds [00382] This invention also is directed, in part, to intermediates that correspond in structure to formula II that can be used to prepare the compounds of formula I (and their saltsXalthough some intermediates can also be used, just like the compounds of formula I, as HCV inhibitors, and one skilled in the art can determine such ability of the compounds of formula II by utilizing, for example, the methods discussed below) (Formula Removed) [00383] In formula n --, R\ R\ R2 R1, and R1 are as discussed above for the compounds of formula I, and X is halo [00384] The various embodiments for :, R\ R2, R2, R4, and R1 (as well as their combinations) discussed above apply to the compounds of formula II Ns to X, in some embodiments, X is selected from the group consisting of chloro, bromo, and lodo In other embodiments, X is selected from the group consisting of chloro and bromo In yet other embodiments, X is selected from the group consisting of chloro and lodo In yet other embodiments, X is selected from the group consisting of lodo and bromo In further embodiments, X is fluoro In yet further embodiments, X is chloro In yet further embodiments, X is bromo Nnd in yet further embodiments, X is lodo [00385]The various embodiments for =-=, R\ R\ R1, R2 R1, and X discussed above can be combined to form various embodiments of compounds of formula 11, and all embodiments of compounds of formula 11 so formed are within the scope of Npplicants invention Some exemplary embodiments of the compounds (and salts thereof) of formula II are discussed below [00386] In some embodiments, the compounds of formula II correspond in structure to formula IIN (Formula Removed) [00387] In other embodiments, the compounds of formula II correspond in structure to formula IIB (Formula Removed) [00388] In some embodiments of the compounds of formula II R1 IS selected from the group consistmg of hydr0gen, methyl, and nitr0gen-protecting group, R2 is selected from the group consisting of hydr0gen and halo, R2 is selected from the group consisting of hydr0gen and halo, R1 is selected from the group consisting of C1-C4-alkyl, Ca-Ce-carbocyclyl, and 5-6-membered heterocyclyl, wherem (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo, oxo, hydroxy, aikyloxy, and trimethylsilyl, and (b) the Cs-Ce-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylammo, R is selected from the group consisting of hydr0gen, hydroxy, aikyloxy, and halo, and X is selected from the group consisting of chloro, bromo, and lodo [00389] In some embodiments of the compounds of formula II =-= is a double carbon-carbon bond. R1 IS hydr0gen, R is selected from the group consisting of hydr0gen and halo, R is hydr0gen, R4 is tert-butyl, R2 is selected from the group consisting of hydr0gen, hydroxy, and methoxy, and X is selected from the group consisting of bromo and lodo [00390] In some embodiments of the compounds of formula II R1 IS selected from the group consisting of hydr0gen and methyl, R2 IS selected from the group consisting of hydr0gen and methyl, R2 IS selected from the group consisting of hydr0gen and methyl, R4 is tert-butyl, R1 IS selected from the group consisting of hydroxy and methoxy, and X IS selected from the group consisting of chloro, bromo, and lodo [00391] In some embodiments of the compounds of formula 11 is a double carbon-carbon bond, R1 IS hydr0gen, R2 is hydr0gen, R2 is hydr0gen, R4 is tert-butyl, R1 IS selected from the group consisting of hydroxy and methoxy, and X is selected from the group consisting of chloro, bromo, and lodo [00392] In some embodiments, the compound of formula II is selected from the group consisting of (Formula Removed) [00393] The discussion below provides instructions for the preparation of intermediate compounds of formula II (and salts thereof) L Starting Compounds [003941 This invention also is directed, m part, to starting compounds that correspond in structure to formula III that can be used to prepare the compounds of formulas II and I (and their salts) (Formula Removed) [00395] In formula III, ==, R1 R\ and R1 are as discussed above for the compounds of formula I and II The various embodiments for =-, R1, R2 and R2 (as well as their combinations) discussed above apply to the compounds of formula ill The various embodiments for , R\ R , and R discussed above can be combined to form various embodiments of compounds of formula III, and all embodiments of compounds of formula III so formed are within the scope of Npplicants invention Some exemplary embodiments of the compounds (and salts thereof) of formula III are discussed below [00396] In some embodiments of the compounds of formula in R1 IS selected from the group consisting of hydr0gen, methyl, and nitr0gen-protecting group, R2 is selected from the group consisting of hydr0gen and halo, and R1 IS selected from the group consisting of hydr0gen and halo [00397] In some embodiments of the compounds of formula III : is a double carbon-carbon bond, R1 IS selected from the group consisting of hydr0gen, R1 is selected from the group consisting of hydr0gen and halo, and R1 is selected from the group consisting of hydr0gen [00398] In some embodiments of the compounds of formula III R1 is selected from the group consisting of hydr0gen and methyl, R1 IS selected from the group consisting of hydr0gen and methyl, and R1 is selected from the group consisting of hydr0gen and methyl [00399] In some embodiments, the compound of formula III is uracil [00400] This invention also is directed, in part, to starting compounds that correspond in structure to formula rv that can be used to prepare the compounds of formulas II and I (and their salts) (FORMULA REMOVED) [00401]In formula IV R , R , and X are as discussed above for the compounds of formula I and 11, and X is halo [00402] The various embodiments for R4, R4, and X (as well as their combinations) discussed above apply to the compounds of formula IV Ns to X, in some embodiments, X is selected from the group consisting of chloro, bromo, and lodo In other embodiments, X is selected from the group consisting of chioro and bromo In yet other embodiments, X is selected from the group consisting of chloro and lodo In yet other embodiments, X is selected from the group consisting of lodo and bromo In further embodiments, X is fluoro In yet further embodiments, X is chloro In yet further embodiments, X is bromo Nnd in yet further embodiments, X is lodo Ns to X and X, in some embodiments, X and X are identical [00403] The various embodiments for R , R2, X , and X discussed above can be combined to form various embodiments of compounds of formula FV, and all embodiments of compounds of formula III so formed are within the scope of Npplicants invention Some exemplary embodiments of the compounds (and salts thereof) of formula IV are discussed below [00404] In some embodiments of the compounds of formula IV R4 is selected from the group consisting of C1-C4-alkyl, C3-C6-carbocycIyI, and 5-6-membercd heterocyclyl, wherein (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and tnmethylsilyl, and (b) the Cs-Ce-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylamino, R1 is selected from the group consisting of hydr0gen, hydroxy, and alkyloxy, X is selected from the group consisting of chloro, bromo, and lodo, and X is selected from the group consisting of chloro, bromo, and lodo [00405] In some embodiments of the compounds of formula IV R4 is selected from the group consisting of tert-butyl, R1 is selected from the group consisting of hydr0gen, hydroxy, and methoxy, X is selected from the group consisting of bromo and lodo, and X is selected from the group consisting of bromo and lodo [00406] In some embodiments of the compounds of formula FV R1 is selected from the group consistmg of tert-butyl, R2 IS selected from the group consisting of hydroxy and methoxy, X is selected from the group consisting of chloro, bromo, and lodo, and X is selected from the group consisting of chloro, bromo, and lodo [00407] In some embodiments of the compounds of formula IV R4 is tert-butyl, R1 IS selected from the group consisting of hydroxy and methoxy X is selected from the group consisting of chloro, bromo, and lodo, and X is selected from the group consisting of chloro, bromo, and lodo [00408] In some embodiments, the compound of formula IV is selected from the group consisting of (Formula Removed) , and [00409] The discussion below provides instructions for the preparation of starting compounds of tormula IV (and salts thereof) L Methods for Preparation [00410] This invention also is directed, in part, to a process for preparing compounds of formula II The process comprises reacting a compound of formula HI with a compound of formula IV in the presence of (i) copper (I) salt catalyst and (u) nitr0genous heteroaryl ligand (Formula Removed) [00411[ In the above process, R1, R2 R2 R4, R4, X\ and X are as discussed above [00412] Npplicants have discovered that the process generally results in the substitution of the Nl hydr0gen of uracil derivative compound III thus resultmg in intermediate compound II When X in intermediate compound II is chloro, bromo, or lodo, then compound II is is suitable for subsequent reaction (e g, Suzuki coupling with an appropriate boronic acid or boronate ester) to provide compound of formula I In other words, when X in intermediate compound 11 is chloro, bromo, or lodo, the above process is suitable for preparing compounds of formula I as well [00413] In some embodiments, compound III is uracil, and compound TV corresponds in structure to a compound selected from the group consisting of compound IV-I, IV-Br, and IV-Cl, with compounds IV- I and rV-Br typically resulting in better yield than compound IV-CI [004141 Suitable Cu(I) catalysts include, for example, Cul, CuBr, CuCl, Cu.O, and CHiC(O)OCu In some embodiments, the catalyst is selected from the group consisting of Cul and CuBr In some such embodiments, the catalyst is Cul In other such embodiments, the catalyst is CuBr [00415] In some embodiments, the process is conducted in the presence of a base In some such embodiments, the base is an inorganic base Suitable inorganic bases include for example, potassium, sodium, and cesium salts (e g, K2CO3, KiP04, Cs2C0i, Na2C03) In some embodiments, the base is selected from the group consisting of potassium salt and cesium salt In some such embodiments, the salt is selected from the group consisting of K3PO4 and CS2CO1 In some embodiments, the base comprises a potassium salt In some such embodiments, the potassium salt is K2CO3 In other such embodiments, the potassium salt is K3PO4 In some embodiments, the base comprises a cesium salt In some such embodiments, the potassium salt is CS2CO3 [00416] Typically, the process is conducted in the presence of a solvent Suitable solvents include, for example, dimethylsulfoxide (DMSO), dimethylformamide (DMF), and acetomtrile (MeCN) In some embodiments, the solvent is DMSO [00417] Typically, the process is conducted at a temperature of from about 40 to about 130°C [00418] In some embodiments, the nitr0genous heteroaryl ligand comprises 8-hydroxyquinoline In other embodiments, the ligand comprises 2-(2-pyridyl)-benzimidazole In yet other embodiments, the ligand comprises a picolinamide compound corresponding m structure to formula V (Formula Removed) [00419] In formula V, R, R1 R1 R1\ R1, R, and R are independently selected from the group consisting of hydr0gen, CM-perfluoroalkyl, CM-alkyloxy, CM-haloalkyI, chloro, or cyano In some embodiments, R, R1 R, R1, R, R, and R are independently selected from the group consisting of hydr0gen, methyl, methoxy, tnfluoromethyl, chloro, and cyano In some embodiments, the ligand of formula V comprises N-(4-cyanophenyl)picolinamide In other embodiments, the ligand of formula V comprises N-(2-cyanophenyl)picolinamide [00420] In some embodiments, the process comprises (a) preparing a compound of formula FV, and (b) reacting a compound of formula III with a compound of formula IV in the presense of (1) copper (I) salt catalyst and (n) nitr0genous heteroaryl ligand, optionally in the presence of inorganic base [00421] Compound of formula FV-I can be prepared by, for example, converting 2-tert-butylphenol into 2-tert-buty 1-4,6-diiodophenol (by, for example, reacting it with Nal and NaOCl), and then converting the 2-tert-butyl-4,6-diiodophenol into l-tert-butyl-3,5-diiod0-2-methoxybenzene (by, for example, treating it with CHI in the presence of a base, such as, for example, NaOH) Mc OMe II-I [00422] Compound of formula FV-Br can be prepared by, for example, converting 2-tert-butylphenol into 2,4-dibrom0-6-tert-butylphenol (by, for example, reactmg it with l,3-dibrom0-5,5-dimethyIimidaz0-lidine-2,4-dione), and then converting the 2,4-dibrom0-6-tert-butylphenol into l,5-dibrom0-3-tert-butyl-2-methoxybenzene (by, for example, treating it with CH3I m the presence of KOtBu) [00423] Ndditional information about the preparation of compounds of formulas I and II (and their salts) is provided in the general discussion andor specific synthesis examples below In the discussion below, R1, R2 R1, R2 R1, L, R2, R2, R2, R, R4, R2, R2 R2, R, R1, R1, R2, X\ and X have the meaning discussed above unless otherwise stated (Formula Removed) [00424] Compound (1-1), wherein R1 is, for example, hydr0gen or -C02Me, and R4 is, for example, hydr0gen or t-butyl, may be treated with nitric acid m solvents such as, for example, acetic acid or water in a temperature range of about 0 to about 35°C over about 1 to about 5h to provide compound (1-2) Compound (1-2) may then be reduced using conditions known to those skilled in the art to furnish the corresponding aniline (1-3) Typical conditions for this reduction include using hydr0gen at a pressure of about 1 to about 5 atmospheres in the presence of a catalyst such as, for example, palladium or platinum on charcoal in a solvent such as, for example, tetrahydrofuran, ethyl acetate, ethanol, or hexane at or near ambient temperature over a period of about 1 to about 12h Dependent on the functional groups present, an alternative reduction procedure may be more appropriate such as, for example, using iron powder in the presence of a mild acid such as, for example, ammonium chloride or dilute hydrochloric acid at reflux temperatures in a mixture of solvents containing, for example, methanol, water, andor tetrahydrofuran over about 1 to about 12h Nnother set of reduction conditions includes the use of sodium borohydnde in a solvent mixture such as, for example, water and tetrahydrofuran Yet another set of reduction conditions includes the use of tin(II) chloride in the presence of hydrochloric acid in such solvents as, for example, water and methanol or mixtures thereof [00425] Compound (1-2) may be modified prior to reduction For example, treatment of compound (1-2), wherein R1 IS hydr0gen, with iodine monochloride in a mixture of methanol and water at or near ambient temperature over a period of about 8 to about 24h supplies compound (1-4), wherein X is iodine Nlternatively, compound (1-2) can be treated with pyridinium hydrobr0mlde perbr0mlde in a solvent such as, for example, acetic acid at or near ambient temperature o\er a period of about 2 to about 16h to provide compound (1-4), wherein X is br0mlne Modifications may be introduced at the phenol moiety in compound (1-4) For example, the phenol may be alkylated with alkyl halides (e g , methyl iodide), alkyl sulfates (e g , methyl sulfate), alkenyl halides (e g, allyl br0mlde), alkynyl halides (e g , propargyl br0mlde) in the presence of a base such as, for example, potassium carbonate in acetone, sodium hydride in dimethylformamide, or potassium t-butoxide in tetrahydrofuran, at temperatures from about 0 to about 35°C over a period of about 1 to about 24h to provide compound (1-5), wherein R is, for example, alkyl, alkenyl, or alkynyl Nlternatively, alkylation may be achieved by using a reagent such as (trimethylsilyl) diazomethane in solvents such as, for example, methanol or t-butyl methyl ether, or mixtures thereof in a sealed tube at or near room temperature over about 8 to about 24h Compound (1-5) may subsequently be reduced to compound (1-6) using the iron powder or tin(II) chloride conditions described above Nn alternative reduction procedure employs hydr0genation at approximately 1 atmosphere pressure with a catalyst such as 5% platinum on sulfided carbon in a solvent such as methanol Protection of the resultant aniline of compound (1-6) with, for example, a t-butyl carbamate can be achieved by treatment with di-tert-butyl dicarbonate in a solvent such as, for example, tetrahydrofuran or dioxane at a temperature of about 50 to about 65°C for about 1 to about 8h provides compound (1-7) [00426] Modifications may also occur at the phenol moiety in compound (1-2) One skilled m the art may alkylate the phenol of compound (1-2) using, for example, the conditions described above to obtain compound (1-8) Compound (1-8) is transformed into compound (1-9) using, for example, one or more of the appropriate reduction conditions described above [00427] Nnother modification of the phenol group in compound (1-2) is sulfonylation to fiimish compound (1-8), wherein R1 is alkylsulfonyl, carbocyclylsulfonyl, or haloalkylsulfonyl Such a compound may be prepared by exposing compound (1-2) to sulfonyl chlorides such as, for example, methanesulfonyl chloride, cyclohexanesulfonyl chloride, benzenesulfonyl chloride, or 3-chloropropane sulfonyl chloride in the presence of a base such as, for example, triethylamine, diisopropylethylamine, or pyndine in a solvent such as, for example, dichloromethane at or near ambient temperature for a period of about 1 to about 24h One skilled in the art can then transform compound (1-8) into compound (1-9) with an appropriate set of reduction conditions (Formula Removed) {00428] Nniline (2-4) can be prepared through use of the Curtius rearrangement To this end, compound (2-1), wherein R4 is not ammo, can be treated in refluxing thionyl chloride with a catalytic amount of dimethylformamide for about 1 to about 4h to obtain acid chloride (2-2) Treatment with thionyl chloride at the reflux temperature in solvents such as, for example, chloroform or toluene also furnishes compound (2-2) Compound (2-2) can be reacted with an aqueous solution of sodium azide in a solvent such as, for example, acetone over about 1 to about 8h to provide acyl azide (2-3) Compound (2-3) can then undergo a Curtius rearrangement in refluxing solvents such as dioxane or toluene The intermediate isocyanate is hydrolyzed with an aqueous acid such as dilute hydrochloric acid in a solvent such as dimethoxyethane to provide compound (2-4) (Formula Removed) [00429] Compound (3-1), wherein R1 IS, for example, hydr0gen, br0mlne, iodine, or -C02Me, can be treated with an acrylic acid either neat at or near ambient temperature in a solvent such as, for example. toluene and heated to reflux over a period of about 15 to about 48h to supply compound (3-2) When excess of an acrylic acid is used, compound (3-3) is produced Compound (3-2) or (3-3) can be treated with urea in a solvent such as for example, acetic acid at about 100 to about 120°C over about 2 to about 48h to supply compound (3-4) (Formula Removed) [00430] Compound (4-2) can be prepared from compound (3-1) dissolved in solvents such as, for example, dimethylformamide or dimethylacetamide by the addition of a benzene solution of (E)-3-methoxyacryloyl isocyanate (prepared as described by Santana, L , et al J Heterocyclic Chem 1999, 36, 293-295 ) at a temperature of about -40 to about -15°C under an inert atmosphere and then warming to ambient temperature for from about 30 mm to about 4h Compound (4-2) can be treated with an acid such as, for example, sulfuric acid in mixtures of water and ethanol in a temperature range of from about 90 to about 110°C for about 1 to about 8h to supply compound (4-3) Nlternatively, compound (4-2) can be cyclized to uracil (4-3) under the basic conditions described by Ueno, Y , et al J Org Chem 70 7925-7935 (2005) (Formula Removed) [00431]Phenol (20-1), wherein R is other than amino, is treated with a source of electrophilic halide, such as, for example, iodine monochlonde to provide dihal0genated compound (20-2), wherein X and X are independently br0mlne or iodine Compound (20-2) is transformed to compound (20-3) by reaction of an alkylating agent such as, for example, methyl sulfate with a base such as, for example, potassium carbonate in refluxing acetone Nlternatively, methjl iodide in the presence of a base such as, for example, potassium -butoxide in a solvent such as, for example, tetrahydrofuran, or dimethylformamide also furnish compound (20-3) In yet another alternative, compound (20-2) can be methylated with (tnmethylsilyl)diazomethane in a solvent such as, for example, t-butyl methyl ether Compound (20-3) can be reacted with uracil, ligand (20-4), copper (I) iodide, and potassium phosphate in dimethyl sulfoxide at about 40°C to about 100°C to supply compound (20-5) [00432] For example, when in compound (20-3), R is tert-butyl, X is lodo, and X is lodo or bromo, compound (20-3) can be stirred with uracil and compound (20-4) in the presence of Cul and K2PO4 in DMSO for about 15 to about 24h at about 60°C to supply compound (20-5) Nlternatives to ligand (20-4) for making (20-5) are 8-hydroxyquinolme and 2-(2-pyridyl)-benzimidazole (Formula Removed) [00433] Compound (25-1) can be br0mlnated by treatment with, for example, pyndinium hydrobr0mlde perbr0mlde in a solvent such as, for example, acetic acid at or near ambient temperature over a period of about 1 to about 8h to give compound (25-2) The amino group of compound (25-2) can be removed by exposure to t-butyl nitrite in a solvent such as, for example, dimethylformamide at a temperature initially at ambient temperature and then increased to the range of about 50 to about 65 °C to give compound (25-3) Ndditional aliquots of t-butyl nitrite can be added at ambient temperature followed by heating until the transformation is complete Compound (25-3) can be reduced to compound (25-4) by, for example, treatment with iron and ammonium chloride (Formula Removed) [00434] Compound (26-1) wherein each Z is independently N or CH can be converted to a boronic acid ester for use m Suzuki reactions For example, compound of formula (26-1) can be converted to compound (26-2), wherein R1 is hydr0gen or methanesulfonyl (when excess methanesulfonyl chloride is used) by treatment with methanesulfonyl chloride m pyridine at approximately ambient temperature m about 1 to about 8h [00435] Compound (26-2) can be transformed to compound of (26-3) by treatment with pinacol-borane in the presence of a catalyst such as, for example, tns(dibenzylidineacetone)dipalIadium (O), hgand such as, for example, tri-t-butylphosphine, and a base such as triethylamine in solvents such as, for example, tetrahydrofuran, dioxane, or toluene at temperatures ranging from ambient to about 130°C [00436] Nlternatively, compound (26-2) can be reacted with bis(pmacolato)diboron in the presence of a catalyst such as, for example, Combiphos® Pd6, dichloro[l,r-bis(diphenylphosphino)ferrocene] palladium (II) dichloromethane adduct, or palladium acetate m the presence of a ligand such as, for example, 2-dicyclohexylphosphin0-2,4,6-trnsopropy1biphenyl (XPhos), and a base such as, for example, potassium acetate in solvents such as, for example, toluene, dioxane, tetrahydrofuran, dimethylformamide or dimethyl sulfoxide in temperatures from about 60 to about 130°C to give compound (26-3) [00437] Compound (26-3) can be converted to protected compound (26-4) by treatment with benzyl chloroformate initially at about 0°C in the presence of saturated aqueous sodium bicarbonate in a mixture of acetone and water This can be warmed to ambient temperature and maintained at that temperature for about 12 to about 24h Subsequently, compound (26-4) can be converted to the boronic acid pinacol ester (26-5) using the reaction conditions described above (Formula Removed) [00438] Compound (26-5), wherein each Z is independently N or CH, can be coupled with compound (1-7) under Suzuki reaction conditions to provide compound (27-3) Such conditions include, for example, use of a palladium catalyst such as, for example, tris(dibenzylidineacetone)palladium (O), palladium acetate, bis(triphenylphosphine)palladium (II) chloride, tetrakis(tnphenylphosphine)palladium, or dichloro[l,r-bis(diphenylphosphino)ferrocene] palladium (II) dichloromethane adduct, base such as, for example, potassium carbonate, potassium phosphate, potassium -butoxide, sodium carbonate, cesium carbonate, or cesium fluoride, and solvent such as, for example, toluene, ethanol, water, or tetrahydrofuran, or mixtures thereof heated in the temperature range from about 40 to about 130°C [00439] Compound (27-3) can be transformed to compound (27-4) in a three-step process The initial step involves removal of the t-butoxycarbonyl protecting group with an acid such as, for example, trifluoroacetic acid m solvent such as, for example, dichloromethane or hydrochloric acid in dioxane at room temperature over about 1 to about 24h Subsequently, the dihydropynmidinedione can be introduced as described in Scheme 3 [00440] Compound (27-5) can be obtained from compound (27-4) in a tw0-step sequence First, the protecting group is removed from the naphthyl amine under reductive conditions Typically, hydr0genation (~1 atmosphere pressure) in the presence of a catalyst such as, for example, 10% palladium on charcoal in a solvent such as, for example, ethyl acetate at or near ambient temperature over a period of about 8 to about 24h Second, the naphthyl amine can now be sulfonylated by treatment with methanesulfonyl chloride in the presence of a base such as triethylamine in a solvent (e g , dichloromethane) at room temperature over about 20 mm to about 4h (Formula Removed) [00441] Compound (28-1), wherein each Z is independently N or CH, and R is, for example, hydr0gen, -NHS02Me, -N(S02Me)2, or methoxy can be coupled with compound (1-7) under Suzuki reaction conditions to provide compound (28-2) Such conditions include, for example, use of palladium catalyst such as, for example, tns(dibenzylidineacetone) palladium (O), palladium acetate, bis(triphenylphosphine)palladium (II) chloride, tetrakis(triphenylphosphine)palIadium, or dichloro[l,r- bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct, a base such as potassium carbonate, potassium phosphate, potassium -butoxide, sodium carbonate, cesium carbonate, or cesium fluoride, and solvent such as, for example, toluene, ethanol, water or tetrahydrofuran, or mixtures thereof heated in the temperature range from about 40 to about 130°C The reaction is typically deoxygenated with an inert gas such as nitr0gen prior to heating The heating may occur in conventional glassware, a sealed tube, or in a microwave reactor over about 1 to about 24h [00442] Compound (28-2) can be transformed to compound (28-3) in a three-step process The initial step involves removal of the t-butoxycarbonyl protecting group with an acid such as, for example, trifluoroacetic acid in solvent such as, for example, dichloromethane or hydrochloric acid in dioxane at room temperature over about 1 to about 24h Subsequently, the uracil can be introduced as described in (Formula Removed) [00443] Compound (28-1), wherein each Z is independently N or CH, and R IS, for example, hydr0gen, -NHS02Me, -N(S02Me)2, or methoxy can be coupled with compound of formula (29-2), wherein X is, for example, br0mlne or lodme, under Suzuki reaction conditions to provide compound of formula (28-3) Such conditions include, for example, use of palladium catalyst such as, for example, tris(diben2ylidineacetone)palladium (O), palladium acetate, bis(tnphenylphosphine)palladium (11) chloride, tetrakis(tnphenylphosphine) palladium , dichloro[l,r-bis(diphenylphosphmo)ferrocene] palladium (II) dichloromethane adduct, or bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane, base such as, for example, potassium carbonate, potassium phosphate, potassium t-butoxide, sodium carbonate, cesium carbonate, or cesium fluoride, and solvent such as, for example, toluene, ethanol, water, or tetrahydrofuran, or mixtures thereof heated in the temperature range from about 40 to about 130°C The reaction is typically deoxygenated with an inert gas such as nitr0gen prior to heating The heating may occur in conventional glassware, a sealed tube, or in a microwave reactor over about 1 to about 24h (Formula Removed) [00444] Compound (30-1), wherein X is br0mlne or iodine, nis 1 or 2, and Z is CH or N, can be reacted with bis(pinacolato)diboron in the presence of a catalyst such as, for example, Combiphos® Pd6, dichloro[l,r-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct, or palladium acetate in the presence of a hgand such as 2-dicyclohexylphosphin0-2,4,6-trusopropy1biphenyl (XPhos), and a base such as potassium acetate m solvents such as, for example, toluene, dioxane, tetrahydrofuran, dimethylformamide or dimethyl sulfoxide in temperatures from 60-130°C to give compound (30-2) The reaction is typically deoxygenated with an inert gas such as nitr0gen prior to heating The heating may occur in conventional glassware, a sealed tube, or in a microwave reactor over 1 to 24h Compound (30-3) can be reacted with compound (30-2) to give compound (30-4) employmg the conditions described in Scheme 11 [00445] Treatment of compound (30-4) with methanesulfonylhydrazide in solvent such as, for example, tetrahydrofuran, methanol, or ethanol, or a mixture thereof at ambient temperature to about 100°C over a period of 8 to 48h provides compound (30-5) (Formula Removed) [00446] Compound (31-1) can be treated with hexamethylditin or hexabutylditin in the presence of a catalyst such as, for example, bis(triphenylphosphine)palIadium (II) chloride in a solvent such as, for example, toluene or dioxane heated to about 50 to about 130°C to supply compound (31-2) Compound (31-2) can be treated with compound (31-3) in presence of catalyst such as, for example, tns(dibenzy-lidine acetone)palladium (O) and hgand such as tn(2-furyl)phosphine in solvent such as, for example, toluene, dioxane, or tetrahydrofuran heated to about 40 to about 130°C to give compound (31-4) (Formula Removed) [00447] Dinitroaniline (34-1) tan be sulfonylated with methanesulfonyl chloride in the presence of a base like, for example, pyridine in a solvent such as, for example, dichloromethane at room temperature over a period of about 8 to about 36h to give compound (34-2) Compound (34-2) can be converted to compound (34-3) using iron powder in the presence of a mild acid such as, for example, ammonium chloride or dilute hydrochloric acid at reflux temperatures in a mixture of solvents, such as, for example, methanol, water, and tetrahydrofuran over about 1 to about 12h (Formula Removed) [00448] Compound (35-1) can be reacted with compound (35-2), wherein Z is O, S, or NH and R1 is hydr0gen, -NHS02Me, or NO2, in the presence of charcoal exposed to air in solvent such as, for example, toluene heated from about 90 to about 110°C for about 24 to about 72h to give compound (35-3) (Formula Removed) [00449] Compound (36-1), wherein Z is O or S, can be reduced to compound (36-2) using iron powder in the presence of a mild acid such as, for example ammonium chloride or dilute hydrochloric acid at temperatures of about 60 to about 90°C in solvents such as, for example, methanol, ethanol, water, and tetrahydrofuran, or mixtures thereof over about 30 min to about 12h Compound (39-2) can be sulfonylated v.ith methdnesulfonyl chloride in the presence of a base like, for example, pyridine in a solvent such as, for example, dichloromethane at room temperature over a period of about 8 to about 36h (Formula Removed) [00450] Compound (37-1) can be sulfonylated with methanesulfonyl chloride in the presence of a base like, for example, pyridine in a solvent such as, for example, dichloromethane at room temperature over a period of about 8 to about 36h to give compound (37-2) Compound (37-2) can be reacted with (4-methoxyphenyl)methanethiol in the presence of a base such as, for example, potassium carbonate m a solvent such as, for example, dimethylformamide heated to about 90 to about 110°C for about 8 to about 24h to give compound (37-3) Compound (37-3) can be reduced to compound (37-4) using iron powder in the presence of a mild acid such as, for example, ammonium chlonde or dilute hydrochloric acid at temperatures of about 60 to about 90°C in solvent such as, for example, methanol, ethanol, water, and tetrahydrofuran, or mixtures thereof over about 30 mm to about 12h Compound (37-4) can be transformed to compound (37-5) in the presence of mercury(II) acetate, anisole, and trifluoroacetic acid at about 0 °C for about 30 to about 90 mm and subsequently bubbling hydr0gen sulfide through the mixture Compound (37-5) can be treated with compound (37-6) in the presence of p-toluenesulfonic acid and triphenylphosphine m a solvent such as, for example, toluene heated to reflux for about 2 to about 16h to supply compound (37-7) (Formula Removed) [00451] Compound (38-1), wherein X is br0mlne or iodine and 7} is O or S, can be reacted with 2,5-hexanedione m the presence of a p-toluenesulfomc acid and pyridine heated in benzene to give compound of formula (38-2) Compound (38-2) can be reacted with bis(pinacolato)diboron m the presence of a catalyst such as, for example, Combiphos® Pd6, dichloro[l,r-bis(diphenylphosphmo)ferrocene] palladium (II) dichloromethane adduct, or palladium acetate in the presence of a ligand such as, for example, 2-dicyclohexylphosphm0-2,4,6-tnisopropy1biphenyl (XPhos), and a base such as, for example, potassium acetate in a solvent such as, for example, toluene, dioxane, tetrahydrofuran, dimethylform-amide or dimethyl sulfoxide at a temperature from about 60 to about 130°C to give compound (38-3) Compound (38-3) can be reacted with compound (38-4) to give compound (38-5) under Suzuki reaction conditions Such conditions include, for example, use of a palladium catalyst such as, for example, dihydr0gen dichlorobis(di-t-butylphosphinit0-KP)palladate(2-), tns(dibenzyhdineacetone) palladium (O), palladium acetate, bis(triphenylphosphine)palladium (II) chloride, tetrakis (tnphenylphosphine)palladium, or dichloro[l,r-bis(diphenylphosphino)ferrocene] palladium (II) dichloromethane adduct, a base such as, for example, potassium acetate, potassium carbonate, potassium phosphate, potassium Nbutoxide, sodium carbonate, cesium carbonate, or cesium fluonde, and solvent such as, for example, toluene, ethanol, water or tetrahydrofuran, or mixtures thereof heated in the temperature range from about 40 to about 130°C [00452] Compound (38-5) can be treated with hydroxylamine hydrochloride in heated ethanol to remove the pyrrole-protecting group Then treatment with methanesulfonyl chloride in the presence of a base such as, for example, pyiidine in a solvent such as, for example, dichloromethane at or near ambient temperature supplies compound (38-6) EXNMPLES [00453] The following examples are merely illustrative, and not limiting to this disclosure in any way [00454] Example N Preparation of (E)-N-(3-tert-butyl-5-iod0-4-methoxyphenylcarbamoyl)-3-methoxy acrylamide (Formula Removed) [00455] Part N Preparation of 2-tert-butyl-4-nitrophenol [00456] To a vigorously stirred solution of 2-tert-butylphenol (l0g, 66 6mmol) in heptane (67ml) was added at a fast drip a solution of 70% nitric acid (4 25ml, 66 6mmol) diluted with water (4 25ml) The resulting dark redbrown mixture was stirred vigorously for 2h The suspended solid was collected by filtration washed with hexane (300mL), water (200mL) and once again with hexane (200mL) to give a cocoa colored powder that was dried to constant mass (4 65g, 35 6%) [00457] Part B Preparation of 2-tert-butyl-6-iod0-4-nitrophenol [00458] To the product from Part N (4 5g, 23 OSmmoI) dissolved m MeOH (120ml) and water (30mL) was added lodme monochloride (I 155ml, 23 OSmmol) drop wise over a penod of 10min The mixture was stirred for 2h and diluted into IL of water and allowed to stand overnight The solid material was collected by filtration and washed 3x50mL with water and dried under vacuum overnight to give a tan solid(7 14g, 96%) [00459] Part C Preparation of 1 -tert-butyl-3-iod0-2-methoxy-5-nitrobenzene [00460]To an ice bath cooled solution ofthe product from Part B (5 5g, 17 13mmol) in MTBE (15ml) in a 50mL pressure vessel was added 2 OM TMS diazomethane (12 85ml, 25 7mmol) followed by drop-wise addition of methanol (1 0ml) resulting in calm bubbling The vessel was sealed and stirred at room temperature for 16h, cooled and the pressure was released The solution was partitioned between EtONc and water The organic layer was washed with 1 OM HCl, saturated potassium carbonate solution, and saturated NaCl The organic layer was dried over sodium sulfate, filtered and concentrated to give a red oil that was used without purification (5 4g, 84%) [00461]Part D Preparation of 3-tert-butyl-5-iod0-4-methoxyaniline [00462]N mixture of the product from Part C (5 80g, 17 Slmmol), ammonium chloride (1 389g, 26 0mmol), and iron (4 83g, 87mmol) in THFMeOHwater (200mL total, 221) was refluxed for 2h, cooled and filtered through Celite The filtrate was evaporated and the residue was partitioned between water and EtONc The organic layer was washed with saturated brine, dried with sodium sulfate, filtered and evaporated to give a brown oil (5 28g, 100% yield) [00463]Part E Preparation of (E)-N-(3-tert-butyl-5-iod0-4-methoxyphenylcarbamoyl)-3-methoxy acrylamide [00464] To a solution of the product from Part E (3 05g, 1 0mmol) in DMF (50ml) at -20°C under N2 was added at a fast drip a 0 4M solution in benzene of (E)-3-methoxyacryloyl isocyanate (50 0ml, 20 00mmol, prepared by the method of Santana et al, J Heterocyclic Chem 36 293 (1999) The solution was stirred for 15min at -20°C, warmed to room temperature for 45min and diluted into EtONc The EtONc layer was washed 4 x 300mL with water, 2 x 100mL with brine, dried (Na2SO4) and concentrated to a brown solid The residue was triturated in Et20hexane to give a fine powder that was collected by filtration and dried to give a tan powder (2 46g, 57%) [00465] Example B Preparation of 1 -(3-tert-butyl-5-iod0-4-methoxyphenyl)dihydropyrimidine-2,4(1 H,3H)-dione (Formula Removed) [00466] To a suspension of the product from Example N (2 46g, 5 69mmol) in ethanol (50ml) was added a solution of 5 5mL of H2SO4 in 50mL water and the mixture was heated at 110°C for 2 5h to give a clear solution The solution was cooled and diluted with 50mL of water while stirring to give an off-white solid that was collected by filtration, washed with water and dried (2 06g, 90%) [00467]Example C Preparation of l-(3-tert-butyl-5-iod0-4-methoxyphenyl)pyrimidine-2,4(lH,3H)-dione (Formula Removed) [00468] Part N Preparation of 2-tert-butyl-4,6-di lodophenol [00469] N solution of 2-tert-butylphenol (20 0g, 133mmol) in methanol (266mL) was treated with sodium hydroxide pellets (6 39g, 160mmol) The mixture was stirred until all the sodium hydroxide had dissolved and was then cooled in an ice-salt bath to -2°C Sodium iodide (15 0g, 100mmol) was added and then 10 % sodium hypochlorite solution (45mL, 73 3mmol) was added drop wise at a rate such that the solution temperature rose no higher than 1 3°C This sequence of events was repeated (3x) until a total of 60g (400mmol) of sodium iodide had been added and the sodium hypochlorite solution was added until the solution color changed from a light green-yellow color to the color of weak iced tea This required all but 16mL of the 180mL total sodium hypochlorite solution measured out With continued cooling at ca 2°C, a solution of sodium thiosulfate pentahydrate (20g) m water (100mL) was added drop wise over 20min Nfter addition, the solution was acidified to pH 3 by drop wise addition of concentrated hydrochloric acid (ca 35mL required of 40mL placed in the addition funnel) The precipitate was collected by filtration and washed with y1 liter of water The salmon-colored solid was sucked as dry as possible, and dried in a vacuum oven at 50°C for 18h These procedures afforded the product (49 61g, 93%) as a tan solid [00470] Part B Preparation of 1 -tert-butyl-3,5-diiod0-2-methoxybenzene [00471] N solution of the product from Part N (20 0g, 49 7mmol) in acetone (140mL) was treated with methyl iodide (3 9mL, 8 83g, 62 2mmol) and 50 % (ww) sodium hydroxide solution (3 02mL, 4 58g, 57 2mmol) followed by stirring at ambient temperature for 48h The mixture was concentrated in vacuo to a volume of ca 50-60mL, followed by dilution with heptane (80mL) and water (50mL) The layers were separated and the organic layer was extracted with saturated sodium chloride solution Drying (Na2SO4) and concentration in vacuo afforded the product (20 59g, 99%) as a light yellow oil [00472]Part C Preparation of 1 -(3-tert-butyl-5-iod0-4-methoxyphenyl)pyrimidine-2,4(IH,3H)-dione [00473] N suspension of the product from Part B (12 04g, 28 9mmol), uracil (3 89g, 34 7mmol), N-(2-cyanophenyl)picolinamide (1 29g, 5 79mmol) andtribasic potassium phosphate (12 9g, 60 8mmol) m DMSO (181mL) was degassed by nitr0gen sparge for 1 h The mixture was then treated with copper (I) iodide (551 mg, 2 89mmol) and degassing was continued for another 10mm The mixture was then warmed at 60°C for 18h The mixture was then poured into water (600mL) and acidified to pH 3 by addition of 4N hydrochloric acid solution The mixture was diluted with ethyl acetate, and the organic layer was extracted with water (3x), saturated ammonium chloride solution (Ix) and saturated sodium chloride solution The solution was dried and treated with (3-mercaptopropyl) silica gel, followed by stirring for 2h The mixture was filtered and concentrated in vacuo The solid obtained was triturated with ether-ethyl acetate (y10 1) and collected by filtration and washed with ether Nfter drying in a vacuum oven at 50°C for 2h, these procedures afforded the product (2 75 g) as a white solid The mother liquors were concentrated in vacuo to afford an amber solid This material was chromat0graphed over a Flash 65 silica gel cartridge, eluting with 20-100 % ethyl acetate in hexanes These procedures afforded a nearly white solid, which was triturated with ether-hexanes and collected by filtration Nfter drying in a vacuum oven for 3h, these procedures afforded another 4 3 Ig of the product as a white solid Total yield 7 06g(61 %) [00474] Example D Preparation of l-(3-ter<-Butyl-5-iod0-4-methoxyphenyl)pyrimidme-2,4(lH,3H)-dione (Formula Removed) [00475] Part N. Preparation of 2-tebutyl-4,6-dllodophenol [00476] 2-rer?-Butylpheaol (99 95g, 665 36mmol) was dissolved m 1250mL methanol and converted to the corresponding phenoxide with 31 96g (799 0mmol, 1 2equiv) of sodium hydroxide by stirring the sodium hydroxide pellets at room temperature, and then cooling the reaction mixture m an icesalt bath Sodium iodide (299 34g, 1997 07mmol, 3 Oequiv) and 8 3% bleach (1265 83g, 1411 39mmol, 2 lequiv) were added to the cold reaction solution in four equal portions, the bleach being added while keeping the reaction mixture at <0°C 500mL of 20% (ww) sodium thiosulfate solution was added over an 18-minute period, with the temperature rising from -0 6°C to 2 5°C The pH of the reaction mixture was adjusted to approximately 3 by adding 197 SmL of cone HCI over a penod of 97min with the reaction temperature going from I 2°C to 4 1°C The resulting slurry was filtered, and the wet cake washed with ~ 2L of water The wet cake was left on the Buchner funnel under vacuum overnight (approximately 15h) to yield 289 33g (potency adjusted yield = 254 61g) of the title product [00477] Part B Preparation of 1 -fe--butyl-3,5-diiod0-2-methoxybenzene [00478] The product from Part N (93%assay, 21 6g, S0mmol) was dissolved in 140mL of acetone Methyl iodide (4 2mL, 67 5mmol, 1 35equiv ) was added, followed by 50% aqueous sodium hydroxide (5 0g, 62 5mmol, 1 25equiv ) The reaction was stirred overnight, then concentrated to approximately 50-60mL 80mL of heptanes was added follov\ed by 50mL of water, and the layers were shaken and separated, and the aqueous layer was back extracted with 20mL of heptanes The organic layers were combined and washed twice with 50mL each of 10% aqueous NaCl to afford 91 1 grams of a heptane solution, which assayed to 19 Ig of the title compound [00479] Part C. Preparation of l-(3-te--Butyl-5-iod0-4-methoxyphenyl)pyrimidine-2,4(lH,3H)-dione [00480] Uracil (33 3g, 297mmol, 1 2equiv ), K3PO4 (106g, 500mmol, 2 lequiv ), Cul (4 6g, 24 2mmol, 0 lequiv ), and N-(2-cyanophenyl)picolinamide (6 4g, 28 7mmol. 0 12equiv ) were charged to a flask and inerted with argon The l-feH-butyl-3,5-diiod0-2-methoxybenzene was solvent switched into MeCN, dissolved in IL DMSO and sparged with argon and added to the solids The reaction was heated to 60°C for 16h Nfter cooling, the reaction was diluted with 2L EtONc and washed with 2 6L water (back extracted with 3 x IL EtONc) The combined organic layers were washed with 2 x IL of 0 25M (CuONc)2 then 2 x 830mL 15% NH4CI then 800mL brine The organic layer was then concentrated and chased with IL heptane, then triturated with refluxing 85 15 (vv) heptane iPrONc for 4h Nfter cooling, the product was collected by filtration and washed with an additional 330mL of 85 15 vv heptanes EtONc to yield after drying 66 9g (70% yield) of the product as a white solid (00481]Example E Preparation of iV-(6-(3-ferr-Butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (Formula Removed) [00482] N solution of 100mL of water and 300mL of THF was sparged with nitr0gen and then transferred via canula and nitr0gen pressure to a flask containing 19 9965g (49 96mmol) of the product from Example D, 20 8234g (59 97mmol, 1 20equivalents) of Nf-(6-(4,4,5,5-tetramethyl-l,3,2-doxaborola-2-yl)naphthalen-2-yI)methanesulfonamlde, and 21 871 Ig (103 03mmol, 2 06equivalents) of potassium phosphate which had been purged with nitr0gen The resulting solution was again sparged with nitr0gen [00483] THF (1 00mL) was sparged with nitr0gen and then transferred via canula and nitr0gen pressure to a flask containing 462 8mg (0 5 Immol, 0 01 equivalents) of Pdidbaj and 735 8mg (2 52mmol, 0 05 equivalents) of l,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane, which had been purged with nitr0gen The resulting solution was again sparged with nitr0gen [00484] The initial THFwater solution was transferred via canula and nitr0gen pressure to the flask containing the catalyst and ligand in THF The reaction was warmed to 50°C and stirred overnight under positive nitr0gen pressure N sample of the reaction was taken the following morning HPLC of the sample showed 0 28 PN% lodouracil starting material, 76 8 PN% product, and 5 2 PN% boronate [00485] The reaction was cooled to room temperature and washed, in three portions, with a solution of 5 84g of L-cysteine and 81 4g of sodium chloride in 550mL of water which had been sparged with nitr0gen The THF solution was filtered through a celite pad The pad was rinsed with 100mL of THF, which was combined with the original THF solution The TFTF solution was concentrated on the rotary evaporator to 136g To the white slurry was added 405mL of ethyl acetate with good agitation The slurry was filtered after stirring overnight The wet cake was washed with 2X50mL of ethyl acetate The solid, an ethyl acetate solvate, was dried in the vacuum oven at 50°C It weighed 25 49g [00486] The solid and 8 7g of 3-mercaptopropyl derivatized silica gel was stirred in 500mL of THF then filtered through a celite pad The filtrate was concentrated on the rotary evaporator to give 13 08g of white solid The solid that had been filtered off on the celite pad was extracted with 500mL of THF at 60°C The THF solution was concentrated to 66g and treated with 206mL of ethyl acetate The solid which precipitated was filtered and dried, yielding 9 13g of product This solid was combined with the original solid and slurried in 100mL of 200 proof 3N ethanol It was filtered and dried in the vacuum oven at 50°C to give 20 74g of product [00487] Example 1 Preparation of N-(6-(3-tert-butyl-5-(2,4-dioxotetrahydropynmidin-1 (2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IN-L0-2.9) (Formula Removed) [00488] Part N Preparation of 6-brom0-2-naphthoic acid [00489] N solution of methyl 6-brom0-2-naphthoate (7 70g, 29 0mmol) in 2 1 THF water (150mL) was treated with lithium hydroxide hydrate (2 44g, 58 Immol) followed by stirring at room temperature for 48h Concentrated under vacuum, diluted with water and cooled to 0C Ncidified to pH3 with 4N HCl Solids were collected by filtration, dissolved m toluene-EtONc (ca 2L) and washed with brine Dried over Na2SO4, filtered and concentrated under vacuum Brown solid was triturated with ether, collected by filtration, and dried under vacuum to give the title compound as a nearly white solid (5 07g, 70%) [004901 Part B Preparation of 6-bromonaphthalen-2-amine [00491] N solution of the product Part N (5 07g, 20 19mmol) and triethylamine (4 22mL, 3 07g, 30 3mmol) in dry DMF (155mL) was treated with the diphenylphosphoroyl azide (6 55mL, 8 34g, 30 3mmol) followed by stirring at room temperature for 3h The solution was then treated with water (20mL) followed by warming at 100°C for 1 h The solution was cooled and the flask fitted with a short-path distillation head and the DMF removed by distillation under high vacuum The solid residue was dissolved in EtONc and washed with saturated sodium bicarbonate solution Filtered through celite and the filtrate was washed with water (3x) and then with brine Dried over Na2SO4, filtered and concentrated under vacuum to give the title compound as a beige solid (4 48g, 100 %) [00492] Part C Preparation of benzyl 6-bromonaphthalen-2-ylcarbamate [00493] N mixture of the product from Part B (1 79g, 8 06mmol) and saturated sodium bicarbonate solution (18mL) in acetone (40mL) at 0 °C was treated drop wise with benzyl chloroformate The mixture was stirred at 0°C for Ih, and then allowed to gradually warm to room temperature over 18h The mixture was diluted with EtONc and water and the layers separated The organic layer was extracted with water and washed with brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave the title compound as a pink solid (1 5g, 52%) [00494| Part D Preparation of benzyl 6-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)naphthalen-2-yl carbamate [00495[ N resealable Schlenk tube containing a solution of the product from Part C (1 42g, 3 99mmol), bis(pinacolato)diboron (1 1 Ig, 4 39mmol), and potassium acetate (I 17g, II 96mmol) in DMF (28mL) was degassed by three freeze-thaw cycles The solution was treated with l,r-bis(diphenyl phosphino)ferrocene palladium (II) chloride dichloromethane complex (98mg, 0 12mmol), followed by degassing by two additional freeze-thaw cycles The Schlenk tube was then sealed and the mixture warmed at 80°C for 18h Cooled and diluted with ethyl acetate and water The mixture was treated with Darco G-60 and then filtered through celite The filtrate was extracted with water (4x) and saturated sodium chloride solution Dried over Na2SO4, filtered and concentrated under vacuum afforded a light brown oil Purification by silica gel column chromat0graphy eluting with EtONchexane gave the title compound as a colorless oil (9I0mg, 57 %) [00496] Part E Preparation of 2-tert-butyI-4-nitrophenol [00497] To a vigorously stirred solution of 2-tert-butylphenol (l0g, 66 6mmol) in heptane (67ml) was added at a fast drip a solution of 70% nitric acid (4 25ml, 66 6mmol) diluted with water (4 25ml) The resulting dark redrown mixture was stirred vigorously for 2h The suspended solid was collected by filtration washed with hexane (300mL), water (200mL) and once again with hexane (200mL) to give a cocoa colored powder that was dried to constant mass (4 65g, 35 6%) [00498] Part F Preparation ot 2-brom0-6-tert-buty 1-4-nitrophenol |00499| N solution of the product from Part E (1 0g, 5 12mmol) in glacial acetic acid (10 25mL) was treated portion wise with pyridine hydrobr0mlde perbr0mlde (1 80g, 5 63mmoI) followed by stirring at room temperature for 2h Ndditional pyndinium hydrobr0mlde perbr0mlde (3 6g) was added in two portions and after another 3h of stirring, the reaction was complete The mixture was poured into ice water, and the mixture treated with a small amount of sodium sulfite The resulting solid was filtered and dried under vacuum to give the title compound as a brown sohd (1 40g, 100 %) [OOSOOJPart G Preparation of l-brom0-3-tert-butyl-2-methoxy-5-nitrobenzene [00501] N solution of the product from Part F (1 40g, 5 1 Immol) in 10 1 t-butylmethylether-methanol (25 5mL) was treated with 2 CM trimethylsilyldiazomethane in ether (5 ImL, 10 21mmol), followed by stirring at room temperature for 18h The mixture was concentrated under vacuum to afford a yellow oil, which was purified by silica gel column chromat0graphy elutmg with EtONchexanes to give the title compound as a yellow oil (1 36g, 92 %) [00502] Part H Preparation of tert-butyl 3-brom0-5-tert-butyl-4-methoxyphenylcarbamate [00503] N solution of the product from Part G (960mg, 3 33mmol) in methanol (17mL) was treated with 5 % platinum on sulfided carbon (100mg), followed by hydr0genation under balloon pressure for 3h, and then filtered through celite and concentrated under vacuum to afford the 3-brom0-5-tert-butyl-4- methoxyaniline as a yellow oil (860mg, 3 33mmol, 100%) N solution of this material in THF (IVmL) was treated with di-tert-butyl dicarbonate (800mg, 3 66mmol) followed by warming at reflux for 2h Concentration under vacuum afforded a beige solid, which was purified by silica gel column chromat0graphy elutmg with EtONchexanes Solid was triturated with hexanes, collected by filtration, and dried under vacuum to give the title compound as a nearly white solid (890mg, 75 %) [00504] Part I Preparation of benzyl 6-(3-tert-butyl-5-(tert-butylcarbamoyl)-2-methoxyphenyl) naphthalen-2-yl carbamate [00505]Toluene (928ul) and EtOH (928ul) were combined with the product from Part H (133mg, 0 37mmol), the product from Part D (299mg, 0 74mmol) and IM sodium carbonate (371ul, 0 37mmol) and de-gassed for 20mm with nitr0gen Tetrakis(triphenylphosphine)palladium(O) (8 6mg, 7 4umol) was added and de-gassing continued 5-10min Heated at 85-90°C for 18h, cooled and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave the title compound (102mg, 49%) [00506] Part J Preparation of benzyl 6-(3 -tert-butyl-5-(2,4-dioxotetrahydropyrimidin-1 (2H)-yl)-2- methoxyphenyl)naphthalen-2-ylcarbamate [00507] N solution of the product from Part I (100mg, 0 18mmol) in CH2CI2 (1 0ml) was treated with trifluoroacetic acid (0 5ml, 6 Smmol) at room temperature for Ih Concentrated under vacuum Dissolved in ethyl acetate, washed with 10% NaHCOs, brine Dried over Na2SO4, filtered and concentrated under vacuum Dissolved in toluene (1 0ml) and added EtsN (25ul, 0 ismmol) and acrylic acid (13ul, 0 19mmol) and the mixture was refluxed for 16h Concentrated under vacuum Dissolved in acetic acid (1 0ml, 17 Smmol) and added urea (11 9mg 0 20mmol) and refluxed for 72h Cooled and poured into ice water, extracted three times with CHCI3, combined extracts, dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave title compound (57 5mg, 58%) [00508]Part K Preparation of N-(6-(3-tert-butyl-5-(2,4-dioxotetrahydropynmidin-l(2H)-yl)-2- methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00509] Combined the product from Part J (56mg, 0 10mmol) and EtONc (1 0ml) and added 10% palladium on carbon (10mg) Stirred under a balloon of H2 gas for 16h Filtered through Celite and concentrated under vacuum Dissolved in CH2CI2 (1 0ml), added Et3N (16ul, 0 11 Smmol) and methanesulfonyl chloride (8 7ul, 0 112mmol) and stirred at room temperature for 30min Concentrated under vacuum and purification by silica gel column chromat0graphy eluting with EtONchexanes gave the title compound (10mg, 20%) H NMR (300 MHz, DMS0-d5) 8 1 34 - 1 48 (m, 9 H) 2 71 (t, J=6 62 Hz, 2 H) 3 08 (s, 3 H) 3 21 (s, 3 H) 3 82 (t, J=6 62 Hz, 2 H) 7 26 (s, 2 H) 7 41 (dd, J8 82, 1 84 Hz, 1 H) 7 59 - 7 76 (m, 2 H) 7 89 - 8 04 (m, 3 H) 10 03 (s, 1 H) 10 34 (s, 1 H), MS (ESI+) mz 496 (M+H), (ES1-) mz 494 (M-H) [00510]Example 2N Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesuIfonamide (compound IB-L0-2.3) (Formula Removed) [005111Part N Preparation of N-(6-bromonaphthalen-2-yl)methanesulfonamide [00512] N solution of the product from Example 1, Part B (4 48g, 20 17mmol) in pyridine (100mL) was treated drop wise with methanesulfonyl chloride (1 97mL, 2 89 g, 25 2mmol) followed by stirring at room temperature for Ih Diluted with toluene and concentrated under vacuum twice The residue was extracted with EtONc and washed with water, IM citric acid and brine Treated with Darco G-60, dried over Na2SO4, filtered through celite and concentrated under vacuum Solid was triturated with ether-hexane, collected by filtration and dried under vacuum to give the title compound as a faint pink solid (3 32g, 55 %) [005l3]Part B Preparation of N-(6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)naphthalen-2-yl) methanesulfonamide [00514] N mixture of the product from Part N (1 00g, 3 33mmoi), bis(pincolato)diboron (1 27g, 5 OOmmoi), potassium acetate (0 98 g, 9 99mmol) and Combiphos Pd6 (84mg, 0 17mmol) in toluene (22mL) was heated at reflux for 3h Cooled and diluted with ethyl acetate and water The mixture was treated with Darco G-60 and filtered through celite The filtrate was washed with water and brine Dried over Na2SO4, filtered and concentrated under vacuum Oil was dissolved m ether and precipitated by addition of hexanes The product was collected by filtration and washed with hexanes Evaporation of the filtrate and purification by silica gel column chromat0graphy eluting with EtONchexanes The title compound fiom crystallization and chromat0graphy was obtained as a white solid (927mg, 80%) 100515] Part C Preparation of tert-butyl 3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen- 2-yl)phenylcarbamate [00516] Combined the product from Example 1, Part H (87mg, 0 243mmol), the product from Part B (169mg, 0 486mmol), toluene (1 0ml), ethanol (1 0ml) and sodium carbonate (0 243ml, 0 243mmol) in a sealed tube and de-gassed with N2 gas for 20min Tetrakis(tnphenylphosphme)palladium(O) (5 61mg, 4 86|amol) was added and de-gassing was continued another 5-10 mm Heated at 90-95°C for 16h Cooled and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave the title compound (92 2mg, 76 %) [00517]Part D Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidm-l(2H)-yl)-2- methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00518] N solution of the product from Part C (90mg, 0 is0mmol) m CH2CI2 (2 0ml) was treated with tnfluoroacetic acid (1 0ml, 12 98mmol) at room temperature for 1 h Concentrated under vacuum, dissolved residue in EtONc, washed with 10% NaHCOa, and brine Dried over Na2SO4, filtered and concentrated under vacuum Dissolved in DMF (1 4ml) and cooled to -25°C and added (E)-3-methoxy- acryloyl isocyanate (0 633ml, 0 361mmol) drop wise while maintaining the temperature below -10°C Warmed to room temperature and stirred for 2h Poured into ether, washed with water, and bnne Dried over Na2SO4, filtered and concentrated under vacuum Ndded a mixture of H2SO4 (0 1ml, 1 876mmol), water (1 0ml) and EtOH (1 0ml) and stirred at 100C I6h Cooled and concentrated under vacuum Poured into water, extracted with EtONc, combined extracts and washed with brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with MeOHCHCl3 gave the title compound (53mg, 59%) H NMR (300 MHz DMS0-d6) 5 1 42 (s, 9 H) 3 08 (s, 3 H) 3 25 (s, 3 H) 5 65 (d, J=7 72 Hz, 1 H) 7 34 (dd, J=15 81,2 57 Hz, 2 H) 7 42 (dd, 8 82, 1 84 Hz, 1 H) 7 65 - 7 76 (m, 2 H) 7 80 (d, 8 09 Hz, 1 H) 7 96 (t, 8 27 Hz, 2 H) 8 02 (s, 1 H) 10 04 (s, 1 H) 11 41 (s, 1 H), MS (ES1 + ) mz 494 (M+H)\ (ESI-) mz 492 (M-H) [00519]Example 2B Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yI)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 3) (Formula Removed) [00520] Part N Preparation of 2-tert-butyl-6-iod0-4-nitrophenol [00521]To the product from Example 1, Part E (4 5g, 23 OSmmol) dissolved in MeOH (120ml) and water (30mL) was added iodine monochlonde (I 155ml, 23 05mmol) drop wise over a period of 10min The mixture was stirred for 2h and diluted into IL of water and allowed to stand overnight The solid material was collected by filtration and washed 3 x 50mL with water and dried under vacuum overnight to give a tan solid (7 14g, 96%) [00522] Part B Preparation of l-tert-butyl-3-iod0-2-methoxy-5-nitrobenzene [00523] To an ice bath cooled solution of the product from Part N (5 5g, 17 13mmoI) m MTBE (15ml) in a 50mL pressure vessel was added 2 OM trimethylsilyl diazomethane (12 85ml, 25 7mmol) followed by drop-wise addition of methanol (1 0ml) resulting in calm bubbling The vessel was sealed and stirred at room temperature for 16h, cooled and the pressure was released The solution was partitioned between EtONc and water The organic layer was washed with 1 OM HCl, saturated potassium carbonate solution, and saturated NaCl The organic layer was dried over sodium sulfate, filtered and concentrated to give a red oil that was used without purification (5 4g, 84%) [00524] Part C Preparation of 3 -tert-buty 1-5 -iod0-4-methoxyanihne [00525] N mixture of the product from Part B (5 80g, 17 31mmol), ammonium chlonde (1 389g, 26 0mmol), and iron (4 83g, 87mmol) in THFMeOHwater (200mL total, 221) was refluxed for 2h, cooled and filtered through Cehte The filtrate was evaporated and the residue was partitioned between water and EtONc The organic layer was washed with saturated brine, dried with sodium sulfate, filtered and evaporated to give a brown oil (5 28g, 100% yield) [00526] Part D Preparation of (E)-N-(3-tert-butyl-5-iod0-4-methoxyphenylcarbamoyl)-3-methoxy acrylamide [00527] To a solution of the product from Part C (3 05g, 1 0mmol) m DMF (50ml) at -20 °C under Nj was added at a fast drip a 0 4M solution m benzene of (E)-3-methoxyacryloyl isocyanate (50 0ml, 20 00mmol, prepared by the method of Santana et al, J Heterocyclic Chem 36 293 (1999) The solution was stirred for 15min at -20 °C, warmed to room temperature for 45min and diluted with EtONc The organic was washed with water and bnne Dried over Na2SO4, filtered and concentrated to a brown solid The residue was triturated in Et20hexane to give a fine powder that was collected by filtration and dried under vacuum to give the title compound as a tan powder (2 46g, 57%) [00528]Part E Preparation of l-(3-tert-butyl-5-iod0-4-methoxyphenyl)dihydropyrimidine-2,4(lH,3H)- dione [00529] To a suspension of the product from Part D (2 46g, 5 69mmoI) in ethanol (50ml) was added a solution of 5 5mL of H2SO4 in 50mL water and the mixture was heated at 110°C for 2 5h to give a clear solution Cooled and diluted with S0ml of water while stirring to give an off-white solid that was collected by filtration, washed with water and dried under vacuum to give the title compound (2 06g, 90%) [00530]Part F Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00531] In a microwave tube, the product from Part E (104mg, 0 26mmol), the product from Example 2N, Parts (108mg, 0 3 Immol), and 1 OM sodium carbonate solution (312)i,L, 0 3 Immol) in 1 1 ethanol- toluene (1 7mL) was degassed by nitr0gen sparge for ismin l,r-Bis(diphenylphosphino) ferrocene palladium (U) chloride dichloromethane complex (9mg, 0 Ollmmol) was added, and degassing was continued for another 5 mm The tube was sealed and heated in the microwave at 100°C for Ih Diluted with dichloromethane and washed with IM citric acid solution and brine The organic layer was then stirred with (3-mercaptopropyl) silica gel for Ih Filtered through celite and concentrated under vacuum Tnturated with ether, methanol, and then again with ether to give the title compound as a nearly white solid(32mg, 25 %) HNMR(300MHz, DMS0-fif«) 8 II 41 (d, J=l 84 Hz, 1 H) 10 04(s, 1 H) 8 03 (s, 1 H) 7 96 (t, J=8 09 Hz, 2 H) 7 80 (d, J=8 09 Hz, 1 H) 7 63 - 7 79 (m, 2 H) 7 35 - 7 45 (m, 1 H) 7 37 (d, J=2 57 Hz, 1 H) 7 32 (d, J=2 57 Hz, 1 H) 5 65 (dd, J=8 09, 2 21 Hz, 1 H) 3 25 (s, 3 H) 3 09 (s, 3 H) 1 43 (s, 9 H) MS (+ESI) mz (rel abundance) 494 (100, M+H), 511 (90, M+NH4), 987 (20,2M+H), 1009 (8, 2M+Na) [00532]Example 3 Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)quinolin-2-yl)methanesulfonamide (compound IB-L0-2.5) [00533] Part N Preparation of (E)-N-(4-bromophenyl)-3-methoxyacrylamide [00534] Combined 4-bromoaniline (285mg, 1 659mmol), CH2CI2 (2 0ml) and pyridine (0 25ml, 09mmol) and slowly added (E)-3-methoxyacryloyl chloride (200mg, 1 659mmol) and stirred at room temperature for 2h The resuhing yellow solid was filtered off and washed with water The solid was dried under vacuum to give the title compound (406mg, 96 %) [00535] Part B Preparation of 6-Bromoquinolin-2( 1 H)-one [00536] The product from Part N (395mg, 1 542mmol) was added in portions to H2SO4 (4 5ml) Stirred for 3h at room temperature, poured onto crushed ice Solid filtered, washed with water and dried under vacuum to give the title compound (203mg, 59 %) [00537JPart C Preparation of 6-brom0-2-chloroquinoline 100538]To phosphorus oxychloride (2 5ml, 26 8mmol) was added, in portions, the product from Part B (200mg, 0 893mmol) Refluxed for Ih, cooled to room temperature and poured onto crushed ice Extracted with CHCI3, extracts combined, dried overmgSO4, filtered and concentrated under vacuum to give the title compound (173mg, 80%) {00539]Part D Preparation of 6-brom0-2-aminoquinoline [00540]The product from Part C (173mg, 0 713mmol), acetamide (843mg, 14 27mmol) and potassium carbonate (493mg, 3 57mmol) were combined and heated at 200 °C for 2h Cooled to room temperature, whereupon it solidified Dissolved m a mixture of CHCI3 and water Nqueous layer was extracted twice more with CHCI3, extracts were combined, washed with bnne, dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy elating with MeOHCHCl3 gave title compound (92mg, 58 %) [00541]Part E Preparation of N-(6-bromoquinolin-2-yl)-N-(methylsulfonyl)methanesulfonamide [00542] Combined the product from Part D (90mg, 0 403mmol) and CH2CI2 (2 0ml) and added triethylamine (0 062ml, 0 444mmol) and methanesulfonyl chloride (0 035ml, 0 444mmol) Stirred at room temperature 16h Ndded triethylamine (0 062ml, 0 444mmol) and methanesulfonyl chloride (0 035ml, 0 444mmol) and stirred at room temperature for Ih Diluted with EtONc, washed with 10% citric acid, 10%y NaHCOa and bnne Dried over Na2SO4, filtered and concentrated under vacuum Dissolved m EtONc and poured into excess hexane Solid collected by filtration to give the title compound (94mg, 61 %y) [00543]Part F Preparation of N-(methylsulfonyl)-N-(6-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) quinolin-2-yl)methanesulfonamide [00544] Combined the product from Part E (94mg, 0 248mmol), bis(pmacolato)diboron (94mg, 0 372mmol), potassium acetate (73 Omg, 0 744mmol), Combi-Phos®PD6 (6 22mg, 0 012mmol) and toluene (1 5ml) and refluxed 18h Cooled to room temperature, diluted with EtONc and water, filtered through Celite, separated the phases, washed the organic phase with brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave title compound (67mg, 63%) [00545]Part G Preparation of N-(6-{3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)quinolin-2-yl)methanesulfonamide [00546J Combined in a microwave tube the product from Example 2B, Part E (27mg, 0 067mmol), the product from Part F (37 4mg, 0 088mmol), ethanol (1 0ml), toluene (1 0ml) and 1M sodium carbonate (0 067ml, 0 067mmol) and the solution was degassed using N2 gas for 20min Tetrakis- (triphenyl-phosphme)palladium(O) (1 559mg, 1 349imol) was added and the solution was degassed an additional 5min The tube was sealed and heated in the microwave at 100C for 45mm Cooled solution diluted with 1 1 EtONc water and filtered through Celite Nqueous layer was extracted twice more with EtONc, combined organic extracts and washed with brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by sihca gel column chromat0graphy eluting with MeOHCHC gave title compound (13 7mg, 41 %) H NMR (300 MHz, CDCI3) 8 1 45 (s, 9 H) 3 18 (s, 3 H) 3 30 (s, 3 H) 5 83 (dd, J=7 91, 2 02 Hz, 1 H) 6 99 (d, J= 8 82 Hz, 1 H) 7 21 (d, J=2 57 Hz, 1 H) 7 36 (d, J=l 11 Hz, 1 H) 7 52 (d, J=8 46 Hz, 1 H) 7 82 - 7 91 (m, 2 H) 7 98 (d, 7=9 19 Hz, 1 H) 8 29 (s, 1 H), MS (ESI+) mz 495 (M+H), (ESI-) mz 493 (M-H) [00547] Example 4 Preparation of (E)-N-(5-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l (2H)-yl)-2-methoxyphenyl)-2,3-dihydr0-1 H-mden-1 -ylidene)methanesulfonohydrazide (compound IB-L0-2.4) (Formula Removed) [00548] Part N Preparation of 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yI)-2,3-dihydr0-lH-mden-l-one [00549] N mixture of 5-brom0-2,3-dihydr0-lH-mden-l-one (2 50g, 11 85mmol), bis(pinacolato) diboron (3 61g, 14 21mmol), potassium acetate (3 49g, 35 5mmol) and Combiphos Pd6 (178mg, 0 36mmol) in toluene (60mL) was heated at reflux for 8h Cooled, diluted with EtONc and extracted with water (2 x) and washed with brine Dried over Na2SO4 and stirred for Ih with (3-mercaptopropyl) silica gel Filtered and concentrated under vacuum to afford a yellow solid Purification by silica gel column chromat0graphy eluting with EtONchexanes gave a yellow solid Triturated with cold hexanes, filtered and dned under vacuum to give the title compound as a fine nearly white solid (1 99g, 65%) N second crop of crystals (140mg) was obtained from the mother liquors, bringing the yield to 70% [00550] Part B Preparation of l-(3-tert-butyl-4-methoxy-5-(l-ox0-2,3-dihydr0-lH-inden-5-yl)phenyI) py nmidine-2,4( 1 H,3 H)-dione [00551] In a microwave tube, a suspension of the product from Example 2B, Part E (I30mg, 0 33mmol), the product from Part N (lOlmg, 0 39mmol), and 1 OM sodium carbonate solution (390nL, 0 39mmol) in 1 1 ethanol-toluene (1 20mL) was degassed by nitr0gen sparge for ismin The mixture was treated with 1 1 -bis(diphenylphosphino)ferrocene palladium (II) chloride dichloromethane complex (13mg, 0 016mmol) and degassing was continued for another 5mm and heated at 100°C in the microwave for Ih Cooled, diluted with EtONc and extracted with IM citric acid solution and brine The organic layer was then stirred with (3-mercaptopropyl) silica gel for 1 h Filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with EtONchexanes gave the title compound as a white solid (80mg, 61 %) [005521PartC Preparation of (E)-N-(5-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxyphenyl)-2,3-dihydr0-lH-inden-l-ylidene)methanesulfonohydrazide [00553] N suspension of the product from Part B (77mg, 0 19mmol) and methanesulfonylhydrazide (22mg, 0 20mmol) in 3 1 THF MeOH (1 9mL) was warmed at 60°C for 24h The mixture was concentrated under vacuum and the residue was purified by silica gel column chromat0graphy eiutmg with EtONchexanes to give the title compound as a white solid (62mg, 66 %) H NMR (300 MHz, DMS0-e) 5 11 40 (d, J=l 84 Hz, 1 H) 9 94 (s, 1 H) 7 76 (dd, J=13 97, 8 09 Hz, 2 H) 7 52 - 7 59 (m, 1 H) 7 51 (d, J=8 46 Hz, 1 H) 7 11 - 7 40 (m, 2 H) 3 28 (s, 3 H) 2 96 - 3 19 (m, 5 H), 2 85 (m, 2 H), 1 40 (s, 9 H) MS (+ESr) mz (rel abundance) 497 (100, M+H), 1015 (5, 2M+Na) [00554]Example 5 Preparation of N-(2-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-I(2H)-yl)-2-methoxyphenyl)benzo[d]oxazol-5-yl)methanesulfonamide (compound IB-L0-2 6) (Formula Removed) [00555] Part N Preparation of methyl 3-tert-butyl-2-hydroxy-5-nitrobenzoate [00556]Methyl 3,5-di-tert-butyI-2-hydroxybenzoate (28 66g, 108 4mmol) was dissolved with stirring in 430mL glacial acetic acid and the resulting mixture was treated drop wise with fuming nitnc acid (90%, 179 26mL) When the addition was complete, the resulting mixture was stirred for 2 5h The reaction mixture was poured into a 2 OL of crushed ice and allowed to stand 30min Nfterwards, 1 OL of water was added and the ice water mixture was allowed to melt The mixture was then filtered, washed with water and dried to provide the title compound (24 57g, 89%) [00557) Part B Preparation of methyl 3-tert-butyl-2-methoxy-5-nitrobenzoate [00558]Methyl 3-tert-butyl-2-hydroxy-5-nitroben7oate (11 41g, 45 0mmol), potassium carbonate(9 34g, 67 6mmol) acetone (200mL), and dimethyl sulfate (6 46g, 67 6mmol) were added t0gether The resultant mixture was then heated to reflux for 16h The mixture was then filtered and the solid was washed with ethyl acetate The resulting organic liquid was then concentrated under vacuum to an oil and redissolved in ethyl acetate (600mL) The organic solution was then washed with water, dried, filtered and concentrated under vacuum to an oil that was then subjected to purification via column chromat0graphy (gradient of 5% to 40% EtONcHexanes) to yield the title compound as an oil (10 42, 87%) [00559] Part C Preparation of methyl 5-amin0-3-tert-butyl-2-methoxybenzoate [00560] Methyl 3-tert-butyl-2-methoxy-5-nitrobenzoate (10 42g, 39 0mmol), iron powder (325mesh, 10 89g, 195mmol), ammonium chloride (3 13g, 58 Smmol), water (30mL), and methanol (150mL) were added t0gether The resultant mixture was then refluxed for Ih The mixture was then cooled to room temperature, filtered through cehte, and the celite washed with methanol The filtrate was then concentrated under vacuum and dissolved in ethyl acetate (600mL) The resultant solution was then washed with water and brine The organic extract was then dried, filtered and concentrated under vacuum to yield the title compound as an oil (9 25g, 100%) [00561] Part D Preparation of (E)-methyl 3-tert-butyl-2-methoxy-5-(3-(3-methoxyacryloyl)ureido) benzoate [00562] The product obtained as described in Part C (2 0g, 8 43mmol) was dissolved m 30mL of N,N- dimethylacetamide and cooled to -25C N 0 SMolar solution of E-3-methoxyacryloyl isocyanate in benzene (21 9mL, 10 96mmol) was added drop wise and the resulting solution was stirred at ambient temperature for 4h, and then poured into water The product was extracted into dichloromethane, washed with brine, dried over sodium sulfate, fihered and evaporated under vacuum to give 100% yield [00563]Part E Preparation of methyl 3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxybenzoate [00564] The product from Part D (3 Ig, 8 Slmmol) was dissolved in ethanol (60mL) Sulfuric acid (6mL) was added to water (60mL) then this solution was added in one portion to the ethanol 1 he heter0geneous mixture was heated at lOCC for 3h The ethanol was removed under vacuum, and then the aqueous solution was extracted with dichloromethane and evaporated to dryness This residue was purified by flash chromat0graphy, eluting with 1% methanoldichloromethane to yield 1 23g (44%) [00565]Part F Preparation of 3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2- methoxybenzoic acid [00566] The product from Part E (1 23g, 3 7mmol) was taken up in ethanol (5mL) and IMolar sodium hydroxide solution (10mL) and stirred at ambient temperature for 18h The solution was diluted with IM HCl and the resulting solid was filtered and dried to give 0 945 g (80%) [005671Part G Preparation of 3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxy benzaldehyde [00568] The product from Part F (0 945g, 2 97mmol) was taken up in thionyl chloride (4 5mL) and the mixture was heated at 80°C for 40min Nfter evaporation to dryness, the acid chloride was dissolved in dry THF (8mL) and cooled to -78°C N IMolar solution of lithium tri-tert-butoxyaluminum hydride in THF (3 0ml, 3 0mmol) was added drop wise Nfter 45min the cold reaction was quenched with IM HCl (5mL), extracted into ethyl acetate, and purified by flash column, eluting with dichloromethane followed by 1% methanoldichloromethane to give 0 635 g (71%) [00569]Part H Preparation of l-(3-tert-butyl-4-methoxy-5-(5-nitrobenzo[d]oxazol-2-yl)phenyl) pyrimidine-2,4( 1 H,3H)-dione [00570]The product from Fart G (400mg, 1 323mmol), 2-amin0-4-nitrophenol (204mg, 1 323mmol), Charcoal (Darco KB, 191mg, 15 88mmol) and toluene (50mL) were added to a flask and the mixture was heated to HOC, and stined open to the air for 48h Filtered through Cehte and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with CH2Cl2MeOH gave the title compound (300mg, 52%) [00571]Part I Preparation of N-(2-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxyphenyl)ben2o[d]oxazol-5-yl)methanesulfonamide [00572] To the product from Part H (300mg, 0 687mmol), iron (192mg, 3 44mmol), and ammonium chloride (55mg, 1 031 mmol) was added to a mixture of THF (15mL), EtOH (15mL) and water (4 5mL) The resultant solution was heated to 90°C for 45min, and cooled Filtered through Celit, washed with ethanol, and concentrated under vacuum The solid was dissolved m ethyl acetate, and washed with water Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with CH2Cl2MeOH provided the aniline The solid (75mg, 0 185mmol) was dissolved in CH2CI2 (5mL), and pyridine (0 045mL, 0 554mmol) and methanesulfonyl chloride (0 025mL, 0 323mmol) were added and stirred at room temperature for 16h CH2CI2 was added followed by washing with a IN HCl Dried over Na2SO4, filtered and concentrated under vacuum Purification by sihca gel column chromat0graphy eluting with CH2Cl2MeOH provided the title compound as a solid (9 8mg, 3%, two steps) IH NMR (300MHz, DMS0-d6) 8 11 46 (s,lH), 9 85 (s,lH), 7 91 (d, J=2 2Hz, IH), 7 81 (dd, J=9 9,8 8Hz, 2H), 7 68 (d, J=2 2Hz, IH), 7 56 (d, J=2 6Hz, IH), 7 33 (dd, J=8 8,1 8Hz, IH), 5 68 (d, J=7 7Hz, IH), 3 64 (s, 3H), 3 00 (s, 3H), 1 42 (s, 9H) MS mz 485 (M+H)+ [00573] Example 6 Preparation of 1 -(3-tert-butyl-4-methoxy-5-(6-nitrobenzo[d]oxazol-2-yI)phenyl) dihydropyrimidme-2,4(lH,3H)-dione (compound IN-L0-2 6) (Formula Removed) [00574] Part N Preparation of 3-(3-tert-butyl-4-metho\y-5-(methoxycarbonyl)phenylamino) propanoic acid [00575] The product from Example 5, Part C (16 44g, 69 3mmol) was dissolved in toluene (200mL) This mixture was heated to reflux and acrylic acid added over time (ImL of acrylic acid added every 3h, 5 23mL total, 76 2mmol) The mixture was then refluxed for 24h The mixture was then cooled and concentrated under vacuum to dryness to yield an oil as the crude title compound that was used directly in the next reaction [00576] Part B Preparation of methyl 3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-1 (2H)-yl)-2- methoxybenzoate [00577] The product from Part N (21 43g, 69 3mmol), urea (10 4g, 173mmol) and acetic acid (glacial, 200mL) were added t0gether The mixture was then heated to 120°C for 18 5h followed by concentration under vacuum to dryness to an oil To this oil was added methanol (13mL), and ethyl acetate (350mL) The resultant mixture was allowed to stand for 24-48h whereby a precipitate formed The resulting solid was filtered off and washed with a small amount of methanol (10mL) and then air dried to yield the title compound as a solid (15 26g, 66%) [00578]Part C Preparation of 3-tert-butyl-5-(2,4-dioxotetrahydropyrimidm-l(2H)-yl)-2-methoxy benzoic acid [00579] The product from Part B (4 52g, 13 52mmol), methanol (70mL), and tetrahydroftiran (70mL) were added t0gether The mixture was then stirred vigorously until a hom0genous solution resulted Once hom0genous, a solution of aqueous sodium hydroxide (1 OM, 68mL) was added The mixture was then stirred for 12h, the mixture was then concentrated under vacuum to remove the organic solvent, followed by the addition of aqueous hydrochloric acid (1 OM, 80mL) that resulted in solid formation The mixture was then concentrated under vacuum To this material was added hydrochloric acid (12M, 1 00mL) and the resultant material heated to 100°C for 1 5h The reaction was then cooled and water added The resulting solid was filtered, washed with water, and dried to yield the title compound as a solid (3 55g, 82%) [00580] Part D Preparation of 3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-2-methoxy benzaldehyde [00581]The product obtained m Part C (4 07g, 12 71mmoi) and thionyl chloride (40 82mL, 559mmol) were combined and the mixture was refluxed for 2h, followed by concentration under vacuum to provide a light yellow colored solid product The solid was dissolved in tetrahydrofuran (I25mL), the solution cooled to -78C and LiNl(0fBu)3 (IM, 14mL) was added slowly over 10min while maintaining the temperature at -78°C The mixture was stirred at 78°C for 2h The reaction was quenched with hydrochloric acid (aq, IM, 25mL) at -78C The mixture was warmed to room temperature and ethyl acetate was added The layers were separated and the aqueous layer was washed with ethyl acetate The organic extracts were combined and washed with half saturated sodium bicarbonate solution The organic layer was dried, filtered and concentrated under vacuum to yield a solid as the title compound (3 73g, 96%) [00582] Part E Preparation of l-(3-tert-butyl-4-methoxy-5-(6-nitrobenzo[d]oxazol-2-yl)phenyl)dihydro pyrimidine-2,4( 1 H,3H)-dione [00583] N mixture of the product from Part D (75mg, 0 246mmol), 2-amin0-5-nitrophenol (38mg, 0 0246mmol) and Darco KB charcoal (excess) was refluxed in toluene (1 0ml) for 24h under exposure to atmospheric of oxygen Cooled, filtered and purified by reverse phase HPLC chromat0graphy eluting with a 40-100% gradient of acetonitrile in water (0 1% TFN) to provide the title compound as a solid (96mg, 64%) H NMR (300 MHz, DMS0-de) 5 1 42 (s, 9 H) 2 74 (t, J=6 80 Hz, 2 H) 3 66 (s, 3 H) 3 82 - 3 88 (m, 2 H) 7 56 (d, J=2 57 Hz, 1 H) 7 91 (d, J=2 57 Hz, 1 H) 8 09 (d, J=8 82 Hz, 1 H) 8 37 (dd, J=8 82,2 21 Hz, 1 H) 8 84 (d, J=2 21 Hz, 1 H) 10 44 (s, 1 H) MS ESU- (439) (M+H)+ [00584]Example 7 Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-1 (2H)-yl)-2-methoxyphenyl)benzo[d]oxazol-6-yl)methanesulfonamide (compound IN-L0-2.5) (Formula Removed) [00585] The product from Example 6 (96mg 0 219mmol) was reacted a iron (0 614g, 1 10mmol), and ammonium chloride (0 176g, 0 329mmol) in the presence of a mixture of tetrahydrofuran (5mL), ethanol (5mL) and water (3mL) The slurry was heated to 90°C for 45min, cooled to ambient temperature Filtered through a pad of celite (l0g), washed with ethanol (20mL), and the filtrate was concentrated under vacuum to a solid The resulting solid was dissolved in ethyl acetate and washed with water Dried over Na2SO4, filtered and concentrated under vacuum to a yellow solid, providing the corresponding aniline The solid was dissolved in dichloromethane (10mL), pyridine (0 670mL, 0 657mmol) and methanesulfonyl chloride (0 221mL, 0 329mmol) were added and the solution stirred at room temperature 16h CH2CI2 was added followed by washing with a IN aq HCl solution Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 98 2 CH2CI2 MeOH gave the title compound as a solid (25mg, 21%, two steps) H NMR (300 MHz, DMS0-dft) 5 1 41 (s, 9 H) 2 73 (t, J=6 62 Hz, 2 H) 3 06 (s, 3 H) 3 61 (s, 3 H) 3 83 (t, J=6 62 Hz, 2 H) 7 28 (dd, J=8 46, 1 84 Hz, 1 H) 7 48 (d, J=2 57 Hz, 1 H) 7 65 (d, J=l 84 Hz, 1 H) 7 80 (d, J=l 47 Hz, 1 H) 7 82 (d, J=4 04 Hz, I H) 10 03 (s, 1 H) 10 41 (s, 1 H) MS ESI+ (487) (M+H)+ [00586] Example 8 Preparation of l-(3-tert-butyl-4-methoxy-5-(5-nitrobenzo[d]oxazol-2-yl)phenyl) dihydropyrimidine-2,4(lH,3H)-dione (compound IN-L0-2 7) (Formula Removed) [00587JThe product from Example 6, Part D (150mg, 0 493mmol) was reacted with 2-amin0-4-nitrophenol (76mg, 0 493mmol) according to the procedures from Example 6, Part E to provide the title compound as a solid (70mg, 32%) H NMR (300 MHz, DMS0-ds) 5 1 42 (s, 9 H) 2 74 (t, J=6 80 Hz, 2 H) 3 65 (s, 3 H) 3 85 (t, J=6 62 Hz, 2 H) 7 55 (d, J=2 57 Hz, 1 H) 7 89 (d, J=2 94 Hz, 1 H) 8 12 (d, J=8 82 Hz, 1 H) 8 40 (dd, J=9 01, 2 39 Hz, 1 H) 8 76 (d, J=2 21 Hz, 1 H) 10 43 (s, 1 H) MS ESI+ (439) (M+H)+ [00588]Example 9 Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-2-methoxyphenyl)benzo[dJoxazol-5-yl)methanesulfonatnide (compound IN-L0-2.8) (Formula Removed) [00589] The product from Example 8 (65mg, 0 148mmol) was reacted according to the procedures from Example 7 to provide the title compound as a solid (42mg, 44%) H NMR (300 MHz, DMS0-dg) 8 141 (s, 9 H) 2 73 (t, J=6 43 Hz, 2 H) 3 01 (s, 3 H) 3 60 (s, 3 H) 3 83 (t, J=6 43 Hz, 2 H) 7 31 (dd, J=8 64, 2 02 Hz, 1 H) 7 49 (d, J=2 94 Hz, 1 H) 7 56 (d, J=2 21 Hz, 1 H) 7 67 (d, J=2 21 Hz, 1 H) 7 81 (s, 1 H) 9 82 (s, 1 H) 10 41 (s, 1 H) MS ES1+ (487) (M+H)+ [00590JExample 10 Preparation of l-(3-(benzo[d]thiazol-2-yl)-5-tert-butyl-4-methoxyphenyI)dihydro pyrimidine-2,4( 1 H,3H)-dione (compound IN-L0-2 3) (Formula Removed) [00591J The product from Example 6, Part D (75mg, 0 246mmol) was reacted with 2-aminobenzene thiol (0 026mL, 0 246mmol) according to the procedures from Example 6, Part E to provide the title compound as a solid (25mg, 25%) H NMR (300 MHz, DMS0-d) 8 1 44 (s, 9 H) 2 73 (t, J=6 43 Hz, 2 H) 3 62 (s, 3 H) 3 84 (t, J=6 62 Hz, 2 H) 7 46 (d, J=2 57 Hz, 1 H) 7 48 - 7 60 (m, 2 H) 7 86 (d, J=2 57 Hz, 1 H) 8 13 (dd, J=l 7 28, 7 72 Hz, 2 H) 10 40 (s, 1 H) MS ESI+ (410) (M+H)+ [00592]Example 11 Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-2-methoxyphenyl)-lH-benzo[d]imidazol-5-yl)methanesulfonamide (compound IN-L0-2 1) (Formula Removed) [00593]Part N Preparation of N-(3,4-dinitrophenyl)methanesulfonamide [00594] N mixture of 3,4-dinitroaniline (5 27g, 28 8mmol), methanesulfonyl chloride (3 36mL, 43 Immol) and pyridine (5 82mL, 71 9mmoI) in CH2CI2 (100mL) was stirred for 24h Mixture was concentrated under vacuum to provide a crude semi-solid title compound that was used without further purification [00595] Part B Preparation of N-(3,4-diaminophenyl)methanesulfonamide [00596] The product from Part N (7 51g, 28 8mmol) was reacted with iron (16g, 288mmol) and NH4CI (3 84g, 71 9mmol) in refluxing CH3OH {1 00mL) and water (20mL) for 2 h Filtered through celite and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with MeOHCH2Cl2 provided the title compound as a dark semi-solid (0 5g, 8%) [00597]Part C Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)-2-methoxy phenyl)-1 H-benzo[d] imidazol-5-yl)methanesulfonamide [00598] N mixture of the product from Example 6, Part D (200mg, 0 657mmol) was reacted with the product from Part B (132mg, 0 657mmol) according to the procedures from Example 6, Part E to provide the title compound as a solid (112mg, 34%) H NMR (300 MHz, DMS0-dg) 8 1 43 (s, 9 H) 2 72 (t, J=6 62 Hz, 2 H) 2 93 (s, 3 H) 3 44 (s, 3 H) 3 82 (t, J=6 43 Hz, 2 H) 7 07 - 7 14 (m, 1 H) 7 38 (d, J=2 57 Hz, 1 H) 7 48 - 7 64 (m, 2 H) 7 72 (d, J=2 57 Hz, 1 H) 9 57 (s, 1 H) 10 38 (s, 1 H) 12 55 (s, 1 H) MS ESI+(486) (M+H)+ [00599] Example 12 Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropyrimidin-l(2H)-y!)-2-methoxyphenyl)benzo[d]thiazol-6-yl)methanesulfonamide (compound IN-L0-2 2) (Formula Removed) [00600] Part N Preparation of N-(3-chlor0-4-nitrophenyl)methanesulfonamide [00601] N mixture of 3-chlor0-4-nitroaniline (4 85g, 28 Immol), methanesulfonyl chloride (3 29mL, 42 2mmol) and pyridine (6 82mL, 84mmol) in THF (100mL) was stirred for 24h Poured in IM HCl (500mL) The resulting precipitate was tillered and air-dried to provide the title compound as a solid (7 03g, 100%) [00602] Part B Preparation of N-(3-(4-methoxybenzylthio)-4-nitrophenyl)methanesulfonamide [00603] N mixture of the product from Part N (7 0g, 27 9mmol), (4-methoxyphenyl)methanethiol (3 89mL, 27 9mmol) and K2CO3 (11 58g, 84mmol) in DMF was heated at 100°C for 12h Cooled and poured into IM HCl (800mL) The resulting precipitate was filtered and air-dried to provide the title compound as a yellow solid (6 98g, 68%) [00604] Part C Preparation of N-(4-amin0-3-(4-methoxybenzylthio)phenyl)methanesulfonamide [00605] The product from Part B (6 98g, 19 0mmol) was reacted according to the procedures from Example 11, Part B to provide the title compound as a yellow semi-solid (4 44 g, 69%) [00606]Part D Preparation of N,N-(3,3-disulfanediy1bis(4-amin0-3,l-phenylene))dimethane-sulfonamide [00607] The product from Part C (708mg, 2 09mmol) was reacted with mercuric (II) acetate (667mg, 2 09mmol), anisole (0 457mL, 4 ismmol) and TFN (10mL) at 0°C for 45min Concentrated under vacuum and dissolved in MeOH Hydr0gen sulfide gas was bubbled into solution for Ih followed by filtration and concentration under vacuum Purification by silica gel chromat0graphy eluting with EtONchexane gave the title compound as a yellowish solid (340mg, 75%) [00608]Part E Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropynmidin-l(2H)-yI)-2-methoxyphenyl)benzo[d]thiazol-6-yl)methanesulfonamide [00609] The product from Part D (1 00mg, 0 23mmol) was reacted with the product from Example 6, Part D (140mg, 0 46mmoI), tnphenylphosphine (60 4mg, 0 23mmol) and 4-methy1benzene- sulfonic acid (0 0054mL, 0 046mmol) in refluxing toluene for 3h Concentrated under vacuum and purified by reverse phase HPLC chromat0graphy eluting a 40-100% gradient of acetonitnle in water (0 1% TFN) to give the title compound as a solid (99mg, 43%) H NMR (300 MHz, DMS0-ds) 5 1 43 (s, 9 H) 2 73 (t, J=6 62 Hz, 2 H) 3 07 (s, 3 H) 3 63 (s, 3 H) 3 83 (t, J=6 62 Hz, 2 H) 7 39 (dd, J=8 82, 2 21 Hz, 1 H) 7 45 (d, J=2 57 Hz, 1 H) 7 83 (d, J=2 57 Hz, 1 H) 7 95 (d, J=2 21 H?, 1 H) 8 05 (d J-8 82 Hz, 1 H) 10 03 (s, 1 H) 10 39 (s, 1 H) MS ES1+ (503) (M+Hyt- [00610] Example 13 Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropynmidin-l(2H)-yl)-2-methoxyphenyl)benzo[d]thiazol-5-yl)methanesulfonamide (compound IN-L0-2 4) (Formula Removed) [0G611]Part N Preparation of N-(4-chlor0-3-nitrophenyl)methanesulfonamide [00612] N mixture of 4-chlor0-3-nitroaniline (5 0g, 29mmol), methanesulfonyl chloride (2 37mL, 30 4mmol) and pyndme (5 9mL, 72 4mmol) in THF (100mL) was stirred for 24h Poured in IM HCl (S00mL) The resulting precipitate was filtered and air-dried to provide the title compound as a solid (6 7g, 92%) [00613]Part B Preparation of N-(4-(4-methoxybenzylthio)-3-nitrophenyl)methanesulfonamide [00614] N mixture of the product from Part N (3 0g, 12mmol), (4-methoxyphenyl)methanethiol (1 67mL, 12mmol) and K2CO3 (4 96g, 36mmol) m DMF was heated at 100°C for 12h Cooled and poured into IM HCl (S00mL) The resulting precipitate was filtered and air-dned to provide the title compound as a yellow solid (1 95g, 44 2%) [00615] Part C Preparation of N-(3-amin0-4-(4-methoxybenzylthio)phenyl)methanesulfonamide [00616] The product from Part B (1 43g, 3 88mmol) was reacted according to the procedures from Example 11, Part B to provide the title compound as a white solid (1 31g, 100%) [00617]Part D Preparation of N,N-(4,4-disulfanediy1bis(3-amin0-4,l-phenylene))dimethane- sulfonamide [00618] The product from Part C (75mg, 0 222mmol) was reacted with mercuric (II) acetate (70 6mg, 0 222mmol), anisole (0 048mL, 0 443mmol) and TFN (10mL) at CC for 45min Concentrated under vacuum and dissolved in MeOH Hydr0gen sulfide gas was bubbled into solution for Ih followed by filtration and concentration under vacuum Purification by silica gel column chromat0graphy eluting with EtONcHexane gave the title compound as a yellowish solid (34mg, 71%) [00619] Part E Preparation of N-(2-(3-tert-butyl-5-(2,4-dioxotetrahydropynmidin-l(2H)-yl)-2-metho\y phenyl)benzo[d]thiazol-5-yl)methanesulfonamide [00620] The product from Part D (50mg, 0 115mmol) was reacted with the product from Example 6, Part D (70mg, 0 230mmol), tnphenylphosphine (30 2mg, 0 1 ismmol) and 4-methy1benzenesulfonic acid (0 00267mL, 0 023mmol) in refluxmg toluene for 3h Concentrated under vacuum and purified by reverse phase HPLC chromat0graphy eluting with a 40-100% gradient of acetonitrile in water (0 1% TFN) to give the title compound as a solid (40mg, 33%) H NMR (300 MHz, DMS0-dg) 5 1 43 (s, 9 H) 2 73 (t, J=6 80 Hz, 2 H) 3 05 (s, 3 H) 3 63 (s, 3 H) 3 84 (t, J=6 62 Hz, 2 H) 7 35 (dd, J=8 64, 2 02 Hz, 1 H) 7 46 (d, J=2 94 Hz, 1 H) 7 86 (d, J=2 94 Hz, 1 H) 7 92 (d, J=l 84 Hz, 1 H) 8 10 (d, J=8 46 Hz, 1 H) 9 98 (s, 1 H) 10 40 (s, 1 H) MS ESI+ (503) (M+H)+ [00621] Example 14 Preparation of l-(3-tert-butyl-4-methoxy-5-(naphthalen-2-yl)phenyl) pyrimidine-2,4(1 H,3H)-dione (compound IB-L0-2 1) (Formula Removed) [00622] Part N Preparation of tert-butyl 3-tert-butyl-4-methoxy-5-(naphthalen-2-yl)phenyl carbamate [00623] In a resealable Schlenk tube, a solution of the product from Example 1, Part H (200mg, 0 56mmol), naphthalene-2-boronic acid (144mg, 0 84mmoI), and 1 OM sodium carbonate solution (558nL, 0 56mmol) in toluene (2 8mL) was degassed by nitr0gen sparge for 10min The mixture was treated with l,r-bis(diphenylphosphino)ferrocene palladium (II) chloride dichloromethane complex (14mg, 0 017mmol) and degassing was continued for another 5min The Schlenk tube was sealed and warmed at 95°C for 18h Cooled and diluted with ethyl acetate and water Treated with Darco G-60 and filtered through cehte Filtrate was extracted with water (2 x) and with brine Dried over Na2SO4, filtered and concentrated Purification by silica gel column chromat0graphy elutmg with 10-75 % EtONc in hexanes gave the title compound as an oil (21 Omg, 93 %) [00624]Part B Preparation of 3-tert-butyl-4-methoxy-5-(naphthalen-2-yl)aniline [00625] The product from Part N (21 Omg, 0 52mmol) was dissolved m 4N HCl in dioxane (4 0ml) and stirred at room temperature for Ih Concentration under vacuum afforded a solid, which was suspended in ethyl acetate and stirred with saturated sodium bicarbonate solution The organic layer was dried over Na2SO4, filtered and concentrated under vacuum to give the title compound, as a brown oil (11 Img, 70 %) [00626]Part C Preparation of (E)-N-(3-tert-butyl-4-methoxy-5-(naphthalen-2-yl)phenylcarbamoyl)-3-methoxyacrylamlde (00627) N solution of the product from Part B (11 Img, 0 36mmol) in dry DMF (2 9mL) at -20C was treated with (E)-3-methoxyacryloyl isocyanate solution (0 66mL, of 0 55M in benzene, 0 36mmol) followed by gradual warming to room temperature Nfter stirring for 30min, the mixture was cooled again to -20°C and more (E)-3-methoxyacryioyl isocyanate solution (1 0ml, 0 55mmol) was added Nfter warming again to room temperature for 30min, the reaction was complete Diluted with EtONc and extracted with water and brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 10-100 % EtONc in hexane gave the title compound as a light yellow oil (144mg, 92%) [00628] Part D Preparation of l-(3-tert-butyl-4-methoxy-5-(naphthalen-2-yl)phenyl)pyrimidine-2,4(1 H,3H)-dione [00629] N suspension of the product from Part C (144mg, 0 33mmol) in 2 2 1 ethanol-water-THf (15mL) was treated with IN sulfuric acid solution (3 0ml) followed by warming at 100°C for 24h Cooled and diluted with EtONc and extracted with water and brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 10-100% EtONc in hexane gave the title compound as a white solid (62mg, 47 %) H NMR (300 MHz, DMS0-di) 6 11 42 (s, 1 H), 8 08 (s, 1 H), 7 90 - 8 04 (m, 3 H), 7 81 (d, J=7 72 Hz, 1 H), 7 72 (d, J=8 46 Hz, 1 H), 7 56 (dd, J=6 25, 3 31 Hz, 2 H), 7 39 (d, J=2 57 Hz, 1 H), 7 33 (d, J=2 57 Hz, 1 H), 5 65 (d, J=7 72 Hz, 1 H), 3 24 (s, 3 H), 1 43 (s, 9 H) MS +ESI mz (rel abundance) 401 (100, M+H), 418 (30, M+NH4) [00630] Example 15 Preparation of l-(3-tert-butyl-4-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl) pynmidine-2,4(lH,3H)-dione (compound IB-L0-2 2) (Formula Removed) [00631] Part N Preparation of tert-butyl 3-tert-butyl-4-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl carbamate [00632]The product from Example 1, Part H (158mg, 0 44mmol) was reacted with 6-methoxy-naphthalen-2-y1boronic acid (107mg, 0 52mmol) according to the procedures from Example 14, Part N to provide the title compound as a white solid (92mg, 47 %) [00633]Part B Preparation of 3-tert-butyl-4-methoxy-5-(6-methoxynaphthalen-2-yl)aniline [00634] The product from Part N (92mg, 0 21mmol) was reacted according to the procedures from Example 14, Part B to provide the title compound as a pink solid (71mg, 99%) [00635] Part C Preparation of (E)-N-(3-tert-butyl-4-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl carbamoyl)-3-methoxyacrylamide [00636[The product from Part B (71mg, 0 21mmol) was reacted according to the procedures from Example 14, Part C to provide the title compound as a buff-colored solid (58mg, 59 %) [00637[ Part D Preparation of l-(3-tert-butyl-4-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl) pyrimidine-2,4( 1 H,3H)-dione [00638] N solution of the product from Part C (58mg, 0 13mmol) in 2 1 1 ethanol-THF-water (4 0ml) was treated with 1 CM sulfuric acid solution (3 0ml) followed by warming at 95°C for 24h Cooled and diluted with EtONc Extracted with water and brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 10-100 % EtONc in hexanes gave the product as a faint pink solid (28mg, 52%) H NN4R (300 MHz, DMS0-c?rt) 5 11 41 (s, 1 H), 8 00 (s, 1 H), 7 91 (dd, J=8 64, 4 60 Hz, 2 H), 7 80 (d, J=7 72 Hz, 1 H), 7 67 (d, J=8 82 Hz, 1 H), 7 34 - 7 47 (m, 2 H), 7 21 - 7 32 (m, 1 H), 7 20 (dd, J=9 01, 2 39 Hz, 1 H), 5 65 (d, J=7 72 Hz, 1 H), 3 90 (s, 3 H), 3 24 (s, 3 H), 1 42 (s, 9 H) MS +ESI mz (rel abundance) 431 (100, M-H), 448 (45, M+NH4) [00639]Example 16 Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl) phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 8) (Formula Removed) [00640] Part N Preparation of 2-brom0-4-tert-butyl-6-nitroaniline [00641] N suspension of 4-tert-butyl-2-nitroaniline (1 033g, 5 32mmol) in glacial acetic acid (7 8mL) was warmed with a heat gun until all solids had dissolved The solution was then cooled and treated portion wise with pyridinium hydrobr0mlde perbr0mlde (1 96g, 6 12mmol) Nfter addition, the solution was stirred at room temperature for Ih The mixture was added to water (S0ml) and treated with a small amount of sodium sulfite Nfter stirring for 30mm, the precipitate was collected by filtration The solid obtained was washed with water and dissolved in EtONc Washed with water and brine Dried over Na2SO4, filtered and concentrated under vacuum to provide the title compound as a yellow-orange solid (136g,94%) [00642]Part B Preparation of l-brom0-3-tert-butyl-5-nitrobenzene [00643] N solution of tert-butyl nitrite (300L of 90%, 261mg, 2 27mmoI) in dry DMF (4mL) was warmed at 50°C and was treated with a solution of the product from Part N (414mg, 1 52mmoI) in DMF (3 5mL) Nfter a few minutes stirring, the solution began to bubble vigorously Nfter warming at 50°C for Ih, additional (300|iL) tert-butyl nitrite was added followed by warming at 50°C for 1 h Nfter 18h at room temperature, tert-butyl nitrite (1 2mL) was added and the mixture warmed at 50°C for 2h Cooled and diluted with EtONc Washed with water and brine Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 5-40 % ethyl acetate in hexanes gave the title compound as a light yellow oil (159mg, 41 %) [00644] Part C Preparation of 3-brom0-5-tert-butylaniline [00645] N solution of the product from Part B (770mg, 2 98mmol) m 3 3 1 methanol-water-THF (14 9mL) was treated with ammonium chloride (239mg, 4 47mmol) and iron powder (833mg, 14 92mmol) followed by warming at reflux for 8h Diluted with EtONc and water and filtered through celite The filtrate was extracted with water and brine Dried over Na2SO4, filtered and concentrated under vacuum to give the title compound as a yellow oil [00646[Part D Preparation of (E)-N-(3-brom0-5-tert-butylphenylcarbamoyl)-3-methoxy acrylamide [006471N solution of the product from Part C (68lmg, 2 99mmol) in dry DMF (23mL) at -30°C was treated drop wise with a 0 4M solution of (E)-3-methoxyacryloyl isocyanate in benzene (14 9mL, 5 96mmol) The solution was stirred at -30°C for 30min followed by warming gradually to room temperature, and then stirred for 18h Diluted with EtONc and washed with water and brine Dried over Na2SO4, filtered and concentrated under vacuum to afford a yellow solid, which was triturated with ether- hexanes and collected by filtration Dried under vacuum to give the title compound as a light brown powder (951mg, 90%) [00648] Part E Preparation of l-(3-brom0-5-tert-butylphenyl)pyrimidine-2,4(l H,3H)-dione [00649] N suspension of the product fi-om Part D (951mg, 2 68mmol) in ethanol (25mL) was treated with a solution of concentrated sulfuric acid (2 60mL, 4 78g, 18 22mmol) in water (13 4mL) followed by warming at 100°C for 1 h Cooled and concentrated to remove ethanol Cooled to 0°C and the precipitate was collected by filtration and washed with water Dried under vacuum to give the title compound as an orange solid (619mg, 72 %) [00650]Part F Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)phenyl) naphthalen-2-yl)methanesulfonamide (006511In a microwave tube, a suspension of the product from Part E (104mg, 0 32mmol), the product from Example 2N, Part B (134mg, 0 39mmol), and 1 OM sodium carbonate solution (386nL, 0 39mmol) in 1 1 ethanol-toluene (2 ImL) was degassed by nitr0gen sparge for 10min The solution was treated with l,r-bis(di-tert-butylphosphino)ferrocene-palladium (II) dichloride (20mg, 0 03 Immol) and degassing was continued for another 5min The mixture was heated at 100°C in the microwave for 30min Diluted with EtONc and washed with watei and brine Dried over Na2SO4 and treated with (3-mercapto propyl) silica gel for 30min Filtered and concentrated under vacuum to afford an amber solid, which was triturated with ether-he\ancs Collected the solid by filtration and dried under vacuum to provide the title compound (81mg, 54 %) H NMR (300 MHz, DMS0-t) 5 11 46 (s, 1 H) 10 05 (s, I H), 8 25 (s, 1 H) 7 98 (dd, J=ll 58, 9 01 Hz, 1 H) 7 86 - 7 93 (m, 1 H) 7 78 - 7 85 (m, 2 H) 7 72 (s, 1 H) 7 67 (s, 1 H) 7 31 - 7 51 (m, 2 H) 5 70 (dd, J=7 72, 2 21 Hz, 1 H) 3 08 (s, 3 H) 1 39 (s, 9 H) [00652]Example 17 Preparation of (E)-N-(5-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)phenyl)-2,3-dihydr0-lH-inden-l-ylidene)methanesulfonohydrazide (compound IB-L0-2 7) (Formula Removed) [00653]Part N Preparation of 1 -(3-tert-butyl-5-(l-ox0-2,3-dihydr0-lH-mden-5-yl)phenyl) pynmidine-2,4(1 H,3H)-dione [00654] In a microwave tube, a suspension of the product from Example 16, Part E, the product from Example 4, Part N (144mg, 0 56mmol), 1 OM sodium carbonate solution (557nL, 0 56mmol) in 1 1 ethanol-toluene (3 0ml) was degassed by nitr0gen sparge for 15min 1, r-Bis(di-t-butylphosphino) ferrocene palladium (II) chloride complex (15mg, 0 023mmol) was added and degassing was continued for an additional 5 mm The tube was sealed and the mixture was heated at 100°C m the microwave for 30 min Diluted with EtONc and water Washed with IM citric acid solution, water, and brine The organic was stirred with (3-mercaptopropyl) silica gel for Ih Dried over Na2SO4, filtered and concentrated under vacuum Purification by silica gel column chromat0graphy eluting with 10-100 % EtONc in hexanes gave the title compound as an off-white solid (86mg, 50 %) [00655] Part B Preparation of (E)-N-(5-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-1 (2H)-yl) phenyl)-2,3-dihydr0-1 H-mden-1 -ylidene)methanesulfonohydrazide [00656JThe product from Part N (80mg, 0 2Immol) was reacted according to the procedures from Example 4, Part C to provide the title compound as a white solid (73mg, 73 %) H NMR (300 MHz, DMS0-Jtf) 5 11 44 (s, 1 H) 9 92 (s, 1 H) 7 64 - 7 98 (m, 5 H) 7 57 (s, 1 H) 7 45 (s, 1 H) 5 68 (d, J=7 72 Hz, 1 H) 3 00 - 3 20 (m, 5 H) 2 85 (d, J=12 50 Hz, 2 H) 1 36 (s, 9 H) MS +ESI mz (rel abundance) 467 (100, M+H) [00657]Example 18 Preparation of N-(6-(3-brom0-5-(2,4-diox0-3,4-dihydropynmidm-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 69) (Formula Removed) [00658] Part N Preparation of 2-brom0-4,6-diiodophenol [00659] N IL round-bottom flask was charged with 2-bromophenol (Nldrich, 8 65g, 50mmol) and methanol (100ml) to give a colorless solution Sodium hydroxide (2 40g, 60 0mmol) was added and stirred until the hydroxide pellets had dissolved The solution was cooled in an ice water bath and sodium iodide (5 6g, 37 4mmol) was added followed by drop-wise addition of sodium hypochlorite (17mL, 27 Smmol) to give a transparent brownred solution and gradual precipitation of a thick, white solid The addition of sodium iodide and bleach was repeated 3 times to give an orange mixture that was stirred for 2h, treated with a solution of sodium thiosulfate in water (20g in 100mL), stirred for I5min and treated drop-wise with concentrated HCI to a constant pH of 1 The mixture was stirred for 15min and filtered to collect a white solid that was washed repeatedly with water and dried to constant mass (14 7g, 69%) [00660] Part B Preparation of 1 -brom0-3,5-diiod0-2-methoxybenzene [00661] N S00mL round-bottom flask was charged with the product from Part N (14 7g, 34 6mmol), lodomethane (2 70ml, 43 3mmol), and sodium hydroxide (2 101ml, 39 Smmol) in acetone (96ml) to give a tan solution The mixture was stirred for 24h and concentrated The residue was dissolved in ethyl acetate, washed with water and saturated sodium chloride, dried over sodium sulfate, filtered and concentrated to give a white solid The solid was recrystalhzed from hot hexane to give a white solid that was collected by filtration (12 3g, 81%) [00662]Part C Preparation of l-(3-brom0-5-iod0-4-methoxyphenyl)pyrimidine-2,4(lH,3H)-dione [00663] N 250mL round-bottom flask was charged with the product from Part B (8 09g, 18 44mmol), pyrimidine-2,4(lH,3H)-dione (2 273g, 20 28mmol), N-(2-cyanophenyl)picolinamide (0 823g, 3 69mmol), copper (I) iodide (0 35 Ig, 1 844mmol) and potassium phosphate (8 22g, 38 7mmol) m DMSO (70ml) The mixture was sealed, sparged with nitr0gen for 15min and heated at 60C for 16h The mixture was partitioned with ethyl acetate and water The organic layer was washed with IM HCI, water, brine, dried with sodium sulfate, and filtered The filtrate was treated with 3-mercaptopropyl flinctionalized silica gel (Nldrich catal0g # 538086), filtered through cehte and evaporated to give an off-white solid (3 92g, 50%) I00664]Part D Preparation of N-(6-(3-brom0-5-(2,4-dio\0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxyphenyI)naphthalen-2-yl)methanesulfonainide [00665] To a 5mL microwave tube was added the product from Part C (212mg, 0 50mmol), the product from Example 2N, Part B (174mg, 0 S0mmol), potassium phosphate (223mg, 1 OSmmol) PN-Ph (CNS 97739-46-3, 4 38mg, 0 OlSmmol) and tris(dibenzylideneacetone)dipalladium(O) (4 58mg, 5 00)imol) in tetrahydrofiiran (3 0ml) and water (1 0ml) The tube was sealed and the mixture was sparged with nitr0gen for 5min and then stirred for 24h The reaction mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel (Nldrich catal0g # 538086), filtered through cehte and evaporated The residue was triturated with methanol CH2CI2 to give the title compound as a white solid (256mg, 51%) H NMR (300 MHz, DMS0-D6) 6 ppm 3 08 (s, 3 H) 3 43 (s, 3 H) 5 68 (d, J=8 09 Hz, 1 H) 7 43 (dd, J=8 82, 2 21 Hz, 1 H) 7 60 (d, J=2 57 Hz, 1 H) 7 72 (m, 2 H) 7 82 (d, J=3 31 Hz, 1 H) 7 84 (d, J=l 84 Hz, 1 H) 7 96 (m, 2 H) 8 09 (s, 1 H) 10 07(s, 1H)11 49 (s, IH) MS (ES1-)wz 513 9, 515 9 (M-H) [00666]Example 19 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(5-methylfuran-2-yl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 58) (Formula Removed) [00667jTo a 5mL microwave tube was added the product of Example 18 (52mg, 0 lOlmmol), 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-l,3,2-dioxaborolane(0 025ml, 0 121mmol), 1,r-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3 28mg, 5 04nmol) and potassium phosphate (42 8mg, 0 201mmol) in THF (3 0ml) and water (1 0ml) The tube was sealed and the mixture was sparged with nitr0gen for 5mm and then heated at SOC for 3h The cooled mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and concentrated The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was purified by reverse phase chromat0graphy to give the desired product as a white solid (23mg, 44%, m p 174-178 ) H NMR (300 MHz, DMS0-D6) 6 ppm 2 38 (s, 3 H) 3 09 (s, 3 H) 3 33 (s, 3 H) 5 69 (dd, J=7 72, 2 21 Hz, 1 H) 6 30 (d, J=3 31 Hz, 1 H) 7 00 (d, J=3 31 Hz, 1 H) 7 43 (m, 2 H) 7 74 (d, J=2 57 Hz, 2 H) 7 78 (dd, J=8 46, 1 84 Hz, 1 H) 7 85 (d, J=8 09 Hz, 1 H) 7 97 (t, J=8 82 Hz, 2 H) 8 12 (s, 1 H) 10 05 (s, I H) 11 46 (d, J=2 21 Hz, 1 H) MS (ESr+) mz 518 (M+H) [006681 Example 20 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxy-3-(thiophen-3-yl)phenyl)naphthalen-2-yI)methanesulfonamide (compound IB-L0-2 53) (Formula Removed) [00669] The title compound was prepared accordmg to the procedure of Example 19 substitutmg thiophen-3-y1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yI)-l,3,2-dioxaborolane to give a white sohd (12mg, 23%) H NMR (300 MHz, DMS0-D6) 5 ppm 3 07 (s, 3 H) 3 22 (s, 3 H) 5 69 (d, J=7 72 Hz, 1 H) 7 41 (dd, J=8 64, 2 02 Hz, 1 H) 7 50 (d, J=2 94 Hz, 1 H) 7 59 (dd, J=5 13, 1 08 Hz, 1 H) 7 69 (m, 3 H) 7 76 (dd, J=8 64, 1 65 Hz, 1 H) 7 89 (d, J=7 72 Hz, 1 H) 7 95 (m, 3 H) 8 09 (s, 1 H) 10 05 (s, 1 H) 11 47 (s, 1 H) MS (ESI+) mz 520 (M+H) [00670] Example 21 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-1 (2H)-yI)-2-methoxy-3-(thiophen-2-yl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 61) (Formula Removed) [00671] The title compound was prepared according to the procedure of Example 19 substituting thiophen-2-y1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylftiran-2-yl)-l,3,2-dioxaborolane to give a white solid (8mg, 15%) H NMR (300 MHz, DMS0-D6) 8 ppm 3 08 (s, 3 H) 3 30 (s, 3 H) 5 70 (d, J=8 09 Hz, 1 H) 7 19 (dd, J=5 33, 3 86 Hz, 1 H) 7 42 (dd, J=8 82, 2 21 Hz, 1 H) 7 49 (d, J=2 57 Hz, 1 H) 7 69 (dd, J=5 15, 1 20 Hz, 1 H) 7 80 (m, 3 H) 7 88 (d, J=7 72 Hz, 1 H) 7 92 (d, J=2 57 Hz, 1 H) 7 98 (m. 2 H) 8 12 (s, 1 H) 10 06 (s, 1 H) 11 48 (s, 1 H) MS (ESI+) mz 520 (M+Hf [00672] Example 22 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-3-(furan-2-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesyulfonamide (compound BB-L0-2 59) (Formula Removed) [00673] The title compound was prepared according to the procedure of Example 19 substituting furan-2-y1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-l ,3,2-dioxaborolane to give a white solid (16mg, 32%) H NMR (300 MHz, DMS0-D6) 8 ppm 3 09 (s, 3 H) 3 35 (s, 3 H) 5 69 (d, J=7 72 Hz, 1 H) 6 69 (dd, J=3 31, 1 84 Hz, 1 H) 7 11 (d, J=3 31 Hz, 1 H) 7 43 (dd, J=8 82, 2 21 Hz, 1 H) 7 49 (d, J=2 94 Hz, 1 H) 7 80 (m, 5 H) 7 96 (m, 2 H) 8 13 (s, 1 H) 10 06 (s, 1 H) 11 47 (s, 1 H) MS (ESI-) mz 502 1 (M-H) [00674]Example 23 Preparation of N-(6-(5-(2,4-dio\0-3,4-dihydropyrimidin-l(2H)-yl)-3-(furan-3-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 64) (Formula Removed) [00675] The title compound was prepared according to the procedure of Example 19 substituting furan-3-y1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-l,3,2-dioxaborolane to give a white solid (6mg, 12%) H NMR (300 MHz, DMS0-D6) 8 ppm 3 09 (s, 3 H) 3 30 (s, 3 H) 5 69 (dd, J=7 71, 1 83 Hz, 1 H) 7 10 (dd, J=l 74, 0 78 Hz, 1 H) 7 42 (dd, J=8 82, 2 21 Hz, 1 H) 7 46 (d, J=2 57 Hz, 1 H) 7 73 (d, J=2 21 Hz, 1 H) 7 76 (d, J=2 57 Hz, 1 H) 7 78 (d, J=l 84 Hz, 1 H) 7 81 (t, J=l 84 Hz, 1 H) 7 86 (d, J=7 72 Hz, 1 H) 7 96 (t, J=8 82 Hz, 2 H) 8 10 (s, 1 H) 8 28 (s, 1 H) 10 05 (s, 1 H) 11 48 (s, 1 H) MS (ESI-) mz 502 1 (M-H) [00676]Example 24 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxy-biphenyl-3-y])naphthalen-2-yl)methanesulfonamide (compound IB-L0-2.71) (Formula Removed) [00677] The title compound was prepared according to the procedure of Example 19 substituting pheny1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-l 3,2-dioxaborolane The crude product was purified by silica gel chromat0graphy eiuting with 3% methanol CH2CI2 to give a white solid (10mg, 8%) H NMR (300 MHz, DMS0-D6) 8 ppm 3 08 (s, 3 H) 3 12 (s, 3 H) 5 69 (dd, J=7 81, 1 47 Hz, 1 H) 7 36 (m, 5 H) 7 56 (d, J=2 57 Hz, 1 H) 7 64 (m, 2 H) 7 74 (d, J=2 21 Hz, 1 H) 7 78 (dd, J=8 46, 1 84 Hz, 1 H) 7 94 (m, 3 H) 8 11 (s, 1 H) 10 04 (s, 1 H) 11 47 (s, 1 H) MS (ESI-) MZ 512 (M-HY [00678]Example 25 Preparation of N-(6-(3-chlor0-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxybiphenyl-3-yl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2.74) (Formula Removed) [00679] The title compound was prepared according to the procedure of Example 19 substituting 3-chloropheny1boronic acid for 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-l,3,2-dioxaborolane to give a white solid (38mg, 68%) H NMR (300 MHz, DMS0-D6) 5 ppm 3 09 (s, 3 H) 3 13 (s, 3 H) 5 70 (dd, J=8 09, 2 21 Hz, 1 H) 7 43 (dd, J=8 82, 2 21 Hz, 1 H) 7 52 (m, 3 H) 7 62 (m, 2 H) 7 72 (m, 2 H) 7 79 (dd, J=8 46, 1 47 Hz, 1 H) 7 95 (m, 3 H) 8 12 (s, 1 H) 10 05 (s, 1 H) 11 47 (d, J=2 21 Hz, 1 H) MS (ESI-) mz 546 (M-H) [00680]Example 26 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(5-methylthiophen-2-yl)phenyl)naphthalen-2-y!)methanesulfonamide (compound IB-L0-2 73) (Formula Removed) [00681] The title compound was prepared according to the procedure of Example 19 substituting 4,4,5,5-tetramethyl-2-(5-methylthiophen-2-yl)-l,3,2-dioxaborolane foR4,4,5,5-tetramethyl-2-(5-methyl-furan-2-yl)-l,3,2-dioxaborolane to give a white solid (22mg, 41%) H NMR (300 MHz, DMS0-D6) 5 ppm 2 49 (s, 3 H) 3 09 (s, 3 H) 3 29 (s, 3 H) 5 69 (dd, J=8 09, 2 21 Hz, 1 H) 6 87 (d, J=2 57 Hz, 1 H) 7 43 (m, 2 H) 7 54 (d, J=3 68 Hz, 1 H) 7 76 (m, 2 H) 7 85 (s, 1 H) 7 87 (d, J=5 15 Hz, 1 H) 7 98 (t, J=9 01 Hz, 2 H) 8 11 (s, 1 H) 10 06 (s, 1 H) 11 47 (d, J=2 21 Hz, 1 H) MS (ESI+) mz 534 (M+H) [00682]Example 27 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-(hydroxy-2-methylpropan-2-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesuIfonamide (compound IB-L0-2.54) (Formula Removed) [00683] Part N Preparation of 2-(2-hydroxy-3,5-diiodophenyl)acetic acid [00684] To a 250mL round bottom flask was added 2-(2-hydroxyphenyl)acetic acid (Nldrich, 3 04g, 20mmol) m acetonitrile (50ml) to give a colorless solution N-iodosuccimide (9 00g, 40 0mmol) was added portionwise over 15min to give a redbrown transparent solution that was stirred for 16h The mixture was concentrated and the resulting solid was triturated in 75mL of water and filtered to collect an orange solid that was dried under vacuum The crude solid was recrystallized from toluene to give a light orange powder (6 0g, 74%) [00685]Part B Preparation of methyl 2-(3,5-diiod0-2-methoxyphenyl)acetate [00686] To a 250mL round-bottom flask was added the product from Part N (6g, 14 85mmol), potassium carbonate (6 16g, 44 6mmol), and dimethyl sulfate (4 12g, 32 7mmol) in acetone (49 5ml) to give a brown suspension Heated at reflux for 16h, cooled, concentrated and the residue was partitioned between EtONc and water The EtONc layer was washed with brine, dried (Na2SO4) and concentrated to a brown oil that was chromat0graphed on a 40g silica cartridge eluting with 3 1 hexaneEtONc to give a yellow oil (6 0g, 94%) [00687] Part C Preparation of methyl 2-(3,5-diiod0-2-methoxyphenyl)-2-methylpropanoate [00688] To a 1 00mL round-bottom flask under nitr0gen was added the product from Part B (1 728g, 4mmol) in anhydrous THF (20ml) and HMPN (2ml) to give a colorless solution Methyl iodide (1 251ml, 20 00mmol) was added and the solution was cooled to -40°C Potassium t-butoxide(12 00ml, 12 00mmol) was added dropwise and the mixture was stirred at -40 to -20°C for B0mln and quenched with IM HCI to a pH of 1 The mixture was extracted 3 X 40ml with EtONc The extracts were combined, washed with brine, dried (Na2SO4) and concentrated The crude product was flash chromat0graphed on a 40g isCO silica cartridge eluting with 9 1 hexaneEtONc to give the bis-methylated product as a yellow oil (1 63g, 89%) [00689] Part D Preparation of 2-(3,5-diiod0-2-methoxyphenyl)-2-methylpropanoic acid [00690] N suspension of the product from Part C (2 63g, 5 72mmol) in MeOH (40ml) and THT (40ml) was treated with 4 OM sodium hydroxide (28ml, 112mmol) and heated at SOC for 48 h The organic solvent was evaporated and the remainmg aqueous solution was acidified with 1M HCI producing a solid that was collected by filtration, washed with water and dried to give the desired carboxyhc acid (2 46g, 96%) [00691] Part E Preparation of 2-(3,5-dnod0-2-methoxyphenyl)-2-methylpropan-1 -ol [00692] N solution of the product from Part D (1 00g, 2 242mmol) m THF (40ml) was treated dropwise with borane THF complex 1 OM (20ml, 20mmol) and then heated at SOC for 24 h The mixture was treated with methanol (20mL), refluxed for 30 min and concentrated The resulting residue was washed with water, brine, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica gel eluting with hexaneEtONc (4 1) to give the desired product (S10mg, 84%) [00693]Part F Preparation of tert-butyl(2-(3,5-diiod0-2-methoxyphenyl)-2-methylpropoxy)- dimethylsilane [00694] N solution of the product from Part E (432mg, 1 O00mmol) in DMF (5ml) was treated with tert- butyldimethylchlorosilane (301mg, 2 O00mmol), and imidazole (204mg, 3 00mmol) and stirred foR2h The mixture was partitioned between IM HCI and ethyl acetate The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica gel eluting with hexaneEtONc (9 1) to give the desired product (522mg, 96%) [00695]Part G Preparation of l-(3-(l-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-iod0-4- methoxyphenyl)pyrimidine-2,4(lH,3H)-dione [00696] TO a 50mL round-bottom flask was added the product from Part F (520mg, 0 952mmol), pyrimidine-2,4(lH,3H)-dione (117mg, 1 047mmol), N-(2-cyanophenyl)picolinamide (42 5mg, 0 190mmol), copper(I) iodide (18 13mg, 0 095mmol) and potassium phosphate (424mg, 1 999mmol) in DMSO (5ml) The vessel was sealed, sparged with nitr0gen and then heated at 60°C for 24h The mixture was partitioned between IM HCl and ethyl acetate The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, and filtered The filtrate was treated with 3- mercaptopropyl functionalized silica gel, filtered and evaporated The residue was chromat0graphed on silica gel eluting with hexaneEtONc (3 2) to give the product as a solid (285mg, 65%) [00697]Part H Preparation of N-(6-(3-(l-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-(2,4- diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00698] To a 5mL microwave tube was added the product from Part G (50mg, 0 094mmol), the product from Example 2N, Part B (32 7mg, 0 094mmol), potassium phosphate (42 Omg, 0 198mmol), PN-Ph (CNS 97739-46-3) (0 827mg, 2 83mol) and tris(dibenzylideneacetone)palladium(O) (0 863mg, 0 943nmol) in THF (3 0ml) and water (1 0ml) The vessel was sealed and the mixture was sparged with nitr0gen for 5min and then heated at 50°C for 2h The mixture was partitioned between IM HCl and ethyl acetate The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was chromat0graphed on sihca gel elutmg with hexaneEtONc (3 7) to give a solid (32mg, 54%) [00699]Part I Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-(l-hydroxy-2- methylpropan-2-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00700] The product from Part H (3 Img, 0 050mmol) in THF (2 0ml) was treated with IM TBNF (0 3ml, 0 3mmol) in THF and stirred overnight The mixture was partitioned with water and ethyl acetate The organic layer was washed with brine three times, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica gel eluting with 2% to 8% methanol in CH2CI2 to give a solid (2Img, 83%) Melting point 256-257°C H NMR (300 MHz, DMS0-D6) S ppm 1 35 (s, 6 H) 3 08 (s, 3 H) 3 23 (s, 3 H) 3 67 (d, J=4 78 Hz, 2 H) 4 72 (t, J=4 78 Hz, 1 H) 5 65 (d, J=8 09 Hz, 1 H) 7 36 (m, 3 H) 7 74 (m, 3 H) 7 98 (m, 3 H) 10 04 (s, 1 H) 11 41 (s, 1 H) MS (ESI+) mz 527 (M+ NH4) [00701]Example 28 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxy-3-(l-methoxy-2-methylpropan-2-yl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 66) (Formula Removed) [00702]Part N Preparation of l,5-diiod0-2-methoxy-3-(l-methoxy-2-methylpropan-2-yl)benzene [00703] To a 25mL round-bottom flask was added the product from Example 27, Part E (259mg, 0 6mmol) and sodium hydride (28 8mg, 1 200mmo!) in THF (5ml) The mixture was stirred for 30min and lodomethane (0 045 1, 0 720mmol) was added The mixture was stirred for 16h and partitioned between ethyl acetate and 1M HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated to give an oil (235mg, 88%) [00704] Part B Preparation of 1 -(3-iod0-4-methoxy-5-( 1 -methoxy-2-methylpropan-2- yl)phenyl)pyrimidine-2,4( I H,3H)-dione [00705] In a 25mL round-bottom flask was added the product from Part N (230mg, 0 516mmol), pyrimidine-2,4(lH,3H)-dione (63 6mg, 0 567mmol), N-(2-cyanophenyl)picolinamide (23 02mg, 0 103mmol), copper(I) iodide (9 82mg, 0 052mmol) and potassium phosphate (230mg, 1 083mmol) in DMSO (5ml) The vessel was sealed, sparged with nitr0gen and heated at 60C for 16h The mixture was cooled and partitioned between ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, bnne, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica gel eluting with 2% to 5% methanol in CH2CI2 to give a solid (140mg, 63%) [00706]Part C Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(l- methoxy-2-methylpropan-2-yl)phenyl)naphthalen-2-yl)methanesulfonamide [00707] In a 5ml microwave tube was added the product from Part B (43mg, 0 1 00mmol), the product from Example 2N, Part B (34 7mg, 0 1 00mmol), potassium phosphate (44 6mg, 0 210mmol), PN-Ph (CNS 97739-46-3) (0 876mg, 3 OOnmol) andtns(dibenzylideneacetone)palladium(O) (0 915mg, 0 999fimol) in THF (3 0ml) and water (1 0ml) The vessel was sealed, sparged with nitr0gen for 5min and heated at 50°C for 2h The mixture was partitioned with ethyl acetate and 1M HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered The filtrate was treated with 3-mercaptopropyl fiinctionalized silica gel, filtered and evaporated The residue was triturated with methanol CH2CI2 (1 1) to give a solid (28mg, 54%) H NMR (300 MHz, DMS0- D6) 5 ppm 1 39 (s, 6 H) 3 08 (s, 3 H) 3 23 (s, 3 H) 3 25 (s, 3 H) 3 61 (s, 2 H) 5 65 (d, J=7 72 Hz, 1 H) 7 27 (d, J=2 57 Hz, 1 H) 7 37 (d, J=2 57 Hz, 1 H) 7 42 (dd, J=8 64, 2 02 Hz, 1 H) 7 69 (dd, J=8 46, 1 84 Hz 1 H) 7 73 (d, J=2 21 Hz, 1 H) 7 78 (d, J=7 72 Hz, 1 H) 7 95 (t, J=8 27 Hz, 2 H) 8 02 (s, 1 H) 10 04 (s, 1 H) 11 41 (s, 1 H) MS (ESI+) mz 541 (M+ NH4) [00708] Example 29 Preparation of methyl 2-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)phenyl)-2-methylpropanoate (compound IB-L0-2 70) (Formula Removed) [00709] Part N Preparation of methyl 2-(5-(2,4-diox0-3,4-dihydropynmidin-1 (2H)-yl)-3-iod0-2-methoxyphenyl)-2-methylpropanoate [00710] To a 100mL round-bottom flask under N2 was added the product from Example 27, Part C (410mg, 0 891mmol), 1 H-pyrimidine-2,4-dione (120mg, 1 069mmol), and potassium phosphate tribasic (397mg, 1 872mmol) in DMSO (5ml) to give a colorless suspension N-(2-cyanophenyl) picolinamide (39 8mg, 0 178mmol) was added and the mix was sparged with N2 for 5min Copper(r) iodide (16 97mg, 0 089mmol) was added and the mix was sparged once again for 1 0mln, placed under N2 and heated at 60°C for 18h The mixture was cooled and partitioned between EtONc and water adjusting the pH to 1 with HCl The aqueous layer was extracted 2X with EtONc The organics were combined, washed with water, saturated NaHCOs, and saturated NaCl The organic layer was dried (Na2SO4), treated with 3-mercaptopropyl functionalized silica, filtered and concentrated The crude product was purified by chromat0graphy on an isCO 40 g silica cartridge eluting with 3% MeOH in CH2CI2 to give a white foam (269mg, 68%) [00711]Part B Preparation of methyl 2-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)phenyl)-2-methylpropanoate [00712] To a 20mL microwave tube was added the product from Part N (0 444g, 1 0mmol), the product from Example 2N, Part B (0 365g, 1 050mmol), and potassium phosphate tribasic (0 446g, 2 100mmol) in 3 1 tetrahydrofiiran-water (12ml) and degassed by nitr0gen sparge for 20min The solution was then treated with PN-Ph (CNS 97739-46-3) (8 77mg, 0 030mmol) and tris(dibenzylidene-acetone)paIladium(O) (9 16mg, 10 OOjimol) followed by degassing for another 5min The microwave tube was then sealed and warmed at 50C for 18h, cooled and partitioned between EtONc and water adjusting the pH to 1 with IM HCl The EtONc layer was washed with water, saturated NaHCOa, and saturated NaCl The organic layer was dried over sodium sulfate, stirred for Ih with 3-mercaptopropyl functionalized silica, filtered and concentrated The crude product was purified by chromat0graphy on an isCO 12g silica cartridge eluting with 1 -3% MeOH in CHjCto give light tan crystals (480mg, 98%) H NMR (300 MHz, DMS0-D6) § ppm 1 52 (s, 6 H) 3 08 (s, 3 H) 3 14 (s, 3 H) 3 64 (s. 3 H) 5 67 (dd, J=8 09, 1 84 Hz, 1 H) 7 37 - 7 48 (m, 3 H) 7 65 (dd, J=8 46, 1 84 Hz, 1 H) 7 73 (d, J=2 21 Hz, 1 H) 7 83 (d, J=8 09 Hz, 1 H) 7 96 (dd, J=8 64, 5 70 Hz, 2 H) 8 01 (s, 1 H) 10 05 (s, 1 H) 11 45 (s, 1 H) MS (ES1-) mz 536 (M-H) (00713JExample 30 Preparation of 2-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)phenyl)-2-methylpropanoic acid (compound IB-L0-2.77) (Formula Removed) [00714] N mixture of the product from Example 29 (108mg, 0 2mmol) and sodium hydroxide (ImL, 4 00mmol) in methanol, THF, water (3 3 1, 10mL) was heated at 80°C for 18h, cooled and carefully acidified to pH 1 with concentrated HCl resulting in the formation of a white precipitate The solid was collected by filtration, washed with water and dried The crude material was triturated in ImL of 1 1 EtONcMeOH, sonicated for 5min and the solid was collected by filtration as a bright white solid (58mg, 54% yield), mp y300°C H NMR (300 MHz, DMS0-D6) 5 ppm 1 50 (s, 6 H) 3 08 (s, 3 H) 3 18 (s, 3 H) 5 66 (d, J-7 72 Hz, 1 H) 7 34 - 7 45 (m, 3 H) 7 67 (dd, J=8 64, 1 65 Hz, 1 H) 7 73 (d, J=l 84 Hz, 1 H) 7 82 (d, J=7 72 Hz, 1 H) 7 96 (dd, J=9 01, 4 60 Hz, 2 H) 8 02 (s, 1 H) 10 04 (s, 1 H) 11 43 (s, 1 H) 12 15 (s, 1 H) MS (ESI-) mz 522 (M-H) [00715] Example 31 Preparation of methyl 5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)benzoate (compound IB-L0-2 72) (Formula Removed) [00716]Part N Preparation of methyl 3,5-diiod0-2-methoxybenzoate [00717] N mixture of 2-hydroxy-3,5-diiodobenzoic acid (3 9g, 10 0mmol) potassium carbonate (4 15g, 30 0mmol) and dimethyl sulfate (2 77g, 22 0mmol) in acetone (33ml) was heated at reflux for 16h, cooled and concentrated The residue was dissolved in EtONc and washed with water, brine, dried (Na2SO4), filtered and concentrated to give an off-white solid (4 2g, quantitative yield) (00718]Part B Preparation of methyl 5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-iod0-2- methoxybenzoate [00719] To a 100mL round-bottom flask under N2 was added the product from Part N (2 09g, 5 0mmol), lH-pyrimidine-2,4-dione (0 67g, 6 0mmol), and potassium phosphate tnbasic (2 2g, 10 5mmol) in DMSO (20ml) to give a colorless suspension N-(2-cyanophenyl)picolmamide (220mg, 1 0mmol) was added and the mix was sparged with N2 for 5min Copper(I) iodide (95mg, 0 5mmol) was added and the mix was sparged once again for 10min, placed under N2 and heated at 60°C for 18h The mixture was cooled and partitioned between EtONc and water adjusting the pH to 1 with HCl The aqueous layer was extracted 2X with EtONc The organics were combined, washed with water, saturated NaHCOa, and saturated NaCl The organic layer was dried (Na2SO4), treated with 3-mercaptopropyl functionahzed silica, filtered and concentrated The crude product was purified by chromat0graphy on an isCO 40g silica cartridge eluting with 3% MeOH in CH2CI2 to give a white foam (1 0g, 50 %) [00720]Part C Preparation of methyl 5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6- (methyIsulfonamido)naphthalen-2-yl)benzoate [00721] N mixture of the product from Part B (101 mg, 0 25mmol), the product from Example 2 N, Part B (91mg, 0 263mmol), and potassium phosphate tribasic (11 Img, 0 525mmol) in 3 1 tetrahydr0-furan- water (12mL) was degassed by nitr0gen sparge for 20min The solution was then treated with PN-Ph (CNS 97739-46-3) (2 192mg, 7 SOnmol) and tris(dibenzylideneacetone)palladium(O) (2 289mg, 2 500|imol) followed by degassing for another 5min The microwave tube was then sealed, warmed at 50°C for 18h, cooled and partitioned between EtONc and water adjusting the pH to 1 with IM HCI The EtONc layer was washed with water, saturated NaHC03, and saturated NaCl The organic layer was dried Na2SO4, stirred for Ih with 3-mercaptopropyl functionalized silica, filtered and concentrated The crude product was purified by chromat0graphy on an isCO 12g silica cartridge eluting with 3% MeOH in CHjClj to give an off-white foam (80mg, 63 %) H NMR (300 MHz, DMS0-D6) 5 ppm 3 09 (s, 3 H) 3 45 (s, 3 H) 3 89 (s, 3 H) 5 69 (d, J=7 72 Hz, 1 H) 7 43 (dd, J=8 82, 2 21 Hz, 1 H) 7 68 - 7 79 (m, 4 H) 7 84 (d, J=7 72 Hz, 1 H) 7 89 - 8 01 (m, 2 H) 8 09 (s, 1 H) 10 06 (s, 1 H) 11 49 (s, 1 H) MS (ESI-) mz 494 (M-Hy [00722]Example 32 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-iod0-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 57) (Formula Removed) [00723]Part N Preparation of 1,3,5-triiod0-2-methoxybenzene [00724] In a 250mL pressure vessel was added 2,4,6-triiodophenol (5g, 10 60mmol) in MTBE (60ml) to give a yellow solution The solution was cooled in an ice bath and 2 OM trimethylsilyldiazomethane (7 95ml, 15 90mmol) was added at a fast drip followed by dropwise addition of methanol (6mL) resulting in calm bubbling The vessel was sealed and stirred at room temperature for 4h The reaction solution was partitioned between EtONc and water and the organic layer was washed with 1M HCl, saturated NaHCOa, and saturated NaCl The EtONc was dried (MgSO4), filtered and concentrated to give a tan solid that was used without purification (4 8g, 94 %) [00725] Part B Preparation of 1 -(3,5-diiod0-4-methoxyphenyl)pyrimidine-2,4( 1 H,3H)-dione [00726] To a 1 00mL round-bottom flask under N2 was added the product from Part N (3 5g, 7 2mmol), lH-pyrimidine-2,4-dione (0 97g, 8 64mmol), and potassium phosphate tribasic (3 2g, 15 0mmol) in DMSO (50ml) to give a colorless suspension N-(2-cyanophenyl)picolinamide (320mg, 1 44mmol) was added and the mix was sparged with N2 for 5min Copper(I) iodide (137mg, 0 72mmol) was added and the mix was sparged once again for 1 0mln, placed under N2 and heated at 60°C for 18h The mixture was cooled and partitioned between EtONc and water adjusting the pH to 1 with HCl The aqueous layer was extracted 2X with EtONc The organics were combined, washed with water, saturated NaHCOs, and saturated NaCl, dried (Na2SO4), treated with 3-mercaptopropyl ftinctionalized silica, filtered and concentrated The resulting solid was triturated in 2 1 hexaneEtONc to give an off white powder (2 2g, 62 %) [00727]Part C Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidm-l(2H)-yl)-3-iod0-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide [00728] N mixture of the product from Part B l-(3,5-diiod0-4-metho\yphenyl)pyrimidine-2,4(lH,3H)-dione (118mg, 0 25mmol), the product from Example 2N, Part B (87mg, 0 25mmol) 1,1-bis(diphenylphosphino)f6rrocene-palladium(II)dichloride CH2CI2 complex (10 21mg, 0 013mmol) and sodium carbonate (0 250ml, 0 25mmol) in toluene (1 0ml) and ethanol (1 0ml) was sparged with nitr0gen for 5mm and microwaved at 100C for 30min The mixture was cooled and partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica elutmg with ethyl acetatehexane (2 3 to 4 1) to give the title compound (16mg, 11%) H NMR (300 MHz, DMS0-D6) 5 ppm 3 08 (s, 3 H) 3 35 (s, 3 H) 5 67 (d, J=8 09 Hz, 1 H) 7 42 (dd, J=8 82,2 21 Hz, 1 H) 7 59 (d, J=2 57 Hz, 1 H) 7 73 (m, 2 H) 7 81 (d, J=8 09 Hz, 1 H) 7 95 (m, 3 H) 8 09 (s, 1 H) 10 06 (s, 1 H) 11 47 (s, 1 H) MS (ESI-) mz 562 (M-H) (00729]Example 33 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxy-3-((tnmethylsilyl)ethynyl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 78) (Formula Removed) [00730] In a 5mL microwave tube were combined ethynyltrimethylsilane (0 044ml, 0 32mmol), the product from Example 32 (45 Img, 0 OSmmol), copper(I) iodide (0 762mg, 4 Opmol), bis(triphenyl-phosphine)palladium(II) chloride (2 81mg, 4 Ojimol) and tnethylamine (0 056ml, 0 40mmol) in acetonitnle (2ml) The mixture was sparged with nitr0gen for 5min, sealed and microwaved at SOC for 20min The reaction mixture was cooled and partitioned with ethyl acetate and water The organic layer was washed with brine, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica elutmg with 1-4% methanol in CH2CI2 to give a solid, (I8mg, 42%) m p 175-nSC H NMR (300 MHz, DMS0-D6) 5 ppm 0 25 (s, 9 H) 3 07 (s, 3 H) 3 65 (s, 3 H) 5 66 (dd, J=7 91, 2 02 Hz, 1 H) 7 41 (dd, J=8 82, 2 21 Hz, 1 H) 7 58 (m, 2 H) 7 69 (dd, J=8 46, 1 84 Hz, 1 H) 7 72 (d, J=2 21 Hz, 1 H) 7 81 (d, 1=1 72 Hz, 1 H) 7 93 (m, 2 H) 8 05 (d, J=l 32 Hz, 1 H) 10 04 (s, 1 H) 11 45 (d, J=2 21 Hz, 1 H) MS (EST+) mz 534 (M+H) 00731]Example 34 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(methylsulfonyl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 68) (Formula Removed) [00732] Part N Preparation of 4-nitrobenzene-2-diaz0-1 -oxide [00733]To a 250mL round-bottom flask was added 2-amin0-4-nitrophenol (6 165g, 40 0mmol) in 48% tetrafluorobonc acid (15ml) Sodium nitrite (2 76g, 40 0mmol) in water (6ml) was added dropwise at OC and the mixture was stirred at room temperature for 30mm The solid was collected by filtration, washed with tetrafluorobonc acid and water The sohd was suspended m acetone (50ml), fihered and dried to give a solid (3 3 Ig, 50%) [00734] Part B Preparation of 2-(methylthio)-4-nitrophenol [00735] To a 1L beaker was added the product from Part N (2 70g, 16 35mmol) in ice water (250g) to give a brown suspension Copper (0 520g, 8 ismmol) was added, followed by addition of sodium thiomethoxide (2 292g, 32 7mmol) m water (50ml) slowly The mixture was stirred at room temperature for 24h The mixture was fikered and the filtrate was acidified with IM HCl producing a solid that was collected by filtration and dried (2 53g, 84%) [00736] Part C Preparation of 2-(methylsulfonyl)-4-nitrophenol 100737]To a 250mL round-bottom flask was added the product from Part B (1 11 Ig, 6 00mmol) in MeOH (20ml) to give a brown suspension Oxone (7 746g, 12 60mmol) in water (20ml) was added slowly at OC The mixture was warmed to room temperature, stirred for Ih and partitioned with ethyl acetate and IM HCl The organic layer was washed with bnne, dried with sodium sulfate, filtered and evaporated The residue was chromat0graphed on silica gel eluting with 1% to 5% methanol in CH2CI2 to give a solid (0 472g, 36%) [00738]Part D Preparation of 2-iod0-6-(methylsulfonyl)-4-nitrophenol [00739] To a 50mL round-bottom flask was added the product from Part C (470mg, 2 164mmol) m MeOH (10ml) and water (2 5ml) Iodine monochloride (0 130ml, 2 60mmol) in CH2CI2 (2 0ml) was added dropwise and the mixture was stirred at room temperature, poured into water (200mL) and stirred for 10min The resulting solid was collected by filtration and dried (636mg, 86%) [00740]Part E Preparation of 1 -iod0-2-methoxy-3-(methylsulfonyl)-5-nitrobenzene 100741]To a 50mL pressure vessel was added the product from Part D (630mg, 1 836mmol) in MTBE (6ml) to give a yellow solution The mixture was cooled in an ice bath and 2M trimethylsilyl- diazomethane (1 377ml, 2 75mmol) was added at a fast drip followed by dropwise addition of MeOH (0 4ml) resulting in calm bubbling The vessel was sealed and stirred at room temperature for Ih The mixture was partitioned with ethyl acetate and IM HCI The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated to give an off-white solid (655mg, 100%) [00742] Part F Preparation of 3-iod0-4-methoxy-5-(methylsuIfonyl)aniline [00743JTO a 250mL round-bottom flask was added the product from Part E (0 650g, 1 820mmol), ammonium chloride (0 146g, 2 73mmoI), and iron (0 508g, 9 10mmol) in THFMeOHwater (50ml, 221) The mixture was refluxed for 2h, cooled and filtered The filtrate was evaporated and the residue was partitioned with ethyl acetate and water The organic layer was washed with brine, dried with sodium sulfate, filtered and evaporated to give a solid (590mg, 99%) [00744]Part G Preparation of (E)-N-(3-iod0-4-methoxy-5-(methylsulfonyl)phenylcarbamoyl)-3- methoxyacrylamide [00745] To a 100mL round-bottom flask was added the product from Part F (500mg, 1 528mmol) in DMF (15 0ml) The solution was cooled under nitr0gen to -20C and (E)-3-methoxyacryloyl isocyanate (15 28ml, 6 1 Immol, prepared as described by Santana, L , et al J Heterocyclic Chem 1999, 36, 293- 295) was added dropwise The mixture was stirred at this temperature for 15min, then warmed to room temperature and stirred for 45min The mixture was diluted with ethyl acetate and washed by water (3 x 50ml), brine (3 x 50ml), dried with sodium sulfate, filtered and evaporated The residue was triturated with ethyl acetatehexane to give a solid (425mg, 61%) [00746]Part H Preparation of 1 -(3-iod0-4-methoxy-5-(methylsulfonyl)phenyl)pyrimidine-2,4(lH,3H)- dione [00747] To a I 00mL round-bottom flask was added the product from Part G (420mg, 0 925mmol) in ethanol (10ml) to give a suspension Concentrated sulfuric acid (ImL, 18 76mmol) in water (10ml) was added and the mixture was heated at 1 lOC for 2h The reaction mix was cooled, diluted with water (50ml) and stirred for 1 0mln The solid material was collected by filtration, washed with water and dried to give a white solid (325mg, 83%) [00748]Part I Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidm-l(2H)-yl)-2-methoxy-3- (methylsulfonyl)phenyl)naphthalen-2-yl)methanesulfonamide [00749] To a 5mL microwave tube was added the product from Part H (63 3mg, 0 15mmol), the product from Example 2N, Part B (52 Img, 0 150mmol), l,r-bis(diphenylphosphino)ferrocene- palladium(II)dichloride complex (6 12mg, 7 50mol) and IM sodium carbonate (0 150ml, 0 is0mmol) in the solvents of toluene (1 0ml) and ethanol (1 0ml) The vessel was sealed and the mixture was sparged with nitr0gen for 5min and microwaved at 1 00C for 30min The mixture was partitioned with ethyl acetate and IM HCI The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated The residue was purified on silica gel eluting with 1% to 8Vo methanol m CH2CI2 to give crude product N final trituration in 1 1 methanoltethyl acetate afforded pure solid (26mg, 34%) H NMR (300 MHz, DMS0-D6) 6 ppm 3 10 (s, 3 H) 3 44 (s, 3 H) 3 45 (s, 3 H) 5 71 (d, J=8 09 Hz, 1 H) 7 44 (dd, J=8 82, 2 21 Hz, 1 H) 7 75 (d, J=l 84 Hz, 1 H) 7 80 (dd, J=8 46, 1 84 Hz, 1 H) 7 86 (d, J=8 09 Hz, 1 H) 7 91 (d, J=2 57 Hz, 1 H) 7 96 (d, J=2 57 Hz, 1 H) 8 00 (m, 2 H) 8 16 (d, J=l 47 Hz, 1 H) 10 10 (s, 1 H) 11 51 (s, 1 H) MS (ESI+) mz 533 (M+NH4) [00750]Example 35 Preparation of N-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)phenyl)methanesulfonamide (compound IB-L0-2 75) (Formula Removed) [00751] Part N Preparation of 2,4-diiod0-6-nitrophenoI [00752]To a solution of 2-nitrophenol (2 78g, 20mmol) in MeOH (120ml) and water (30mL) was added dropwise a solution of iodine monochlonde (2 105ml, 42 0mmol) in 10mL CH2CI2 The mixture was stirred for 2h, poured into 600mL water, stirred and sonicated for 30mm The mixture was filtered to collect a yellow solid that was washed 3x with water (50mL each wash) and dried to constant mass (7 3g, 93%) m [00753] Part B Preparation of 1,5-diiod0-2-methoxy-3-nitrobenzene [00754] N 50mL pressure vessel was charged with the product from Part N and MTBE (10ml) to give a yellow solution The solution was cooled in an ice bath and 2M trimethylsilyldiazomethane (2 251ml, 4 50mmol) was added at a fast drop followed by dropwise addition of MeOH (0 6ml) resulting in calm bubbling The vessel was sealed and stirred allowing warm to room temperature over 4h The mixture was partitioned with ethyl acetate and IM HCI The organic layer was washed with saturated sodium bicarbonate, bnne, dned with sodium sulfate, filtered and evaporated to give a yellow solid (1 22g, [00755]Part C Preparation of 3,5-diiod0-2-methoxyaniline [00756] In a 250 round-bottom flask was added the product from Part B (0 98g, 2 420mmol), ammonium chloride (0 194g, 3 63inmol), and iron (0 676g, 12 10mmol) in THFmethanolwater (20ml20ml10ml) The mixture was refluxed for 16ho, cooled and filtered The filtrate was evaporated and the residue was partitioned with water and ethyl acetate The organic layer was dried with sodium sulfate, filtered and evaporated to give an oil (780mg, 86%) [00757]Part D Preparation of l-(3-amin0-5-iod0-4-methoxyphenyl)pynmidine-2,4(lH,3H)-dione [00758] In a 25mL round-bottom flask was added the product from Part C (650mg, 1 734mmol), pyrimidine-2,4(lH,3H)-dione (214mg, 1 907mmol), N-(2-cyanophenyl)picoIinamide (77mg, 0 347mmol), copper(I) iodide (33 Omg, 0 173mmol) and potassium phosphate (773mg, 3 64mmol) in DMSO (5ml) The vessel was sealed and the mixture was sparged with nitr0gen for 15min and heated at 60C for 16h The mixture was partitioned with ethyl acetate and 1M HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was chromat0graphed on silica eluting with 5 95 methanolD CH2CI2CM to give a solid (125mg, 20%) I00759]Part E Preparation of N-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-iod0-2-methoxy-phenyl)methanesulfonamide [00760] N solution of the product from Part D (1 10mg, 0 306mmol) in pyridine (2ml) was treated with methanesulfonyl chloride (0 048ml, 0 612mmol) and stirred for 24h The solvent was evaporated and the residue was partitioned with ethyl acetate and IM HCl The organic layer was washed with brine, dried with sodium sulfate, filtered and evaporated The residue was purified on silica gel eluting with 2% to 5% methanol in CHjCb to give a solid (20mg, 15%) [007611Part F Preparation of N-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(6-(methylsulfonamido)naphthalen-2-yl)phenyl)methanesulfonamide 100762] To a 5mL microwave tube was added the product from Part E (18mg, 0 041 mmol), Example 2N, Part B (14 30mg, 0 041mmol), potassium phosphate (18 35mg, 0 086mmol), PN-Ph (CNS 97739-46-3) (0 361mg, 1 235|imol) and tns(dibenzyhdeneacetone)dipalladium(O) (0 377mg, 0 412nmol) in THF (3 0ml) and water (1 0ml) The vessel was sealed and the mixture was sparged with nitr0gen for 5min and heated at 50C for 2h The mixture was partitioned with ethyl acetate and 1M HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate, filtered and evaporated The residue was punfied on silica gel eluting with 2% to 5% methanol in CH2CI2 to give a solid N final trituration in 1 1 methanol CH2CI2 gave the desired product (7mg, 32%) H NMR (300 MHz, DMS0-D6) 5 ppm 3 09 (s, 3 H) 3 17 (s, 3 H) 3 37 (s, 3 H) 5 69 (dd, J=7 91, 2 02 Hz, 1 H) 7 34 (d, J=2 57 Hz, 1 H) 7 43 (dd, J=8 82, 2 21 Hz, 1 H) 7 47 (d, J=2 57 Hz, 1 H) 7 73 (m, 2 H) 7 81 (d, J=8 09 Hz, 1 H) 7 94 (d, J=6 25 Hz, 1 H) 7 97 (d, J=6 62 Hz, 1 H) 8 07 (s, 1 H) 9 45 (s, 1 H) 10 05 (s, 1 H) 11 45 (d, J=l 84 Hz, 1 H) MS (ES1-) mz 529 (M-H) [00763]Example 36 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(trifluoromethyl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 56) (Formula Removed) [00764] Part N Preparation of 4-iod0-2-(trifluoromethyl)phenol [00765] To a solution of 2-(trifluoromethyl) phenol (3 24g, 20mmol) in MeOH (40ml) was added sodium hydroxide (0 960g, 24 0mmol) and stirred until the hydroxide was dissolved The mixture was cooled to OC and sodium iodide was added (3 0g, 20mmol) followed by dropwise addition of 10% aqueous sodium hypochlorite (9 0ml, 14 6mmoI) The addition of sodium iodide followed by sodium hypochlorite was repeated twice more The mixture was stirred at ambient temperature for 2h and treated dropwise with concentrated HCl to pH I The mixture was extracted 3 X with EtONc The extracts were combined, washed with brine, dried with sodium sulfate, filtered and evaporated The residue was purified on silica gel eluting with EtONchexane (1 9) to give the mon0-iodo product (5 0 g, 87%) [00766] Part B Preparation of 2-brom0-4-iod0-6-(trifluoromethyl)phenol [00767] In a 250niL round-bottom flask was added the product from Part N (5 00g, 17 36mmol) and 1,3- dibrom0-5,-dimethylhydantoin (2 73g, 9 55mmol) in CHCI3 (80ml) to give an orange solution The mixture was stirred for 2h, washed with water, brine, dried with sodium sulfate, filtered and evaporated The crude product was purified on silica gel eluting with ethyl acetatehexane (5 95) to give a solid (3 5g, 54%) [00768] Part C Preparation of 1 -brom0-5-iod0-2-methoxy-3-(trifluoromethyl)benzene [00769] N mixture of the product from Part B (3 2g, 8 72mmol), lodomethane (1 36ml, 21 8mmol), and 50% sodium hydroxide (0 507ml, 9 59mmol) m acetone (20ml) was stirred for 24h The solvent was evaporated and the residue was partitioned with ethyl acetate and water The organic layer was washed with brine, dried with sodium sulfate, filtered and evaporated The crude material was purified on silica gel eluting with ethyl acetatehexane (5 95) to give a solid (2 67g, 80%) [00770] Part D Preparation of 1 -(3-brom0-4-methoxy-5-(trifluoromethyl)phenyl)pyrimidine-2,4 (lH,3H)-dione [00771] In a 20mL microwave tube was added the product from Part C (762mg, 2 0mmol), pyrimidine- 2,4(1 H,3H)-dione (247mg, 2 2mmol), N-(2-cyanophenyl)picolinamide (89mg, 0 4mmol), copper(I) iodide (38 Img, 0 2mmol) and potassium phosphate (892mg, 4 2mmol) in DMSO (10ml) The vessel was sealed and the mixture was sparged with nitr0gen for 15min and heated at 60C for 16h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was purified on silica gel eluting with ethyl acetatehexane (2 3) to give the desired product (63mg, 9%) [00772]Part E Preparation of N-(6-(5-(2,4-dio\0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(tnfluoromethyl)phenyl)naphthalen-2-yl)methanesulfonamide [00773] In a 5mL microwave tube was added the product from Part D (60mg, 0 164mmol), the product from Example 2N, Part B (62 8mg, 0 181 mmol), 1,1 -bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 36mg, 8 22nmol) and potassium phosphate (69 8mg, 0 329mmol) in THFwater (3mllml) The vessel was sealed and the mixture was sparged with nitr0gen for 5min and heated at 60C for 2h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was purified by reverse phase chromat0graphy to give the title compound as a solid (26mg, 31%) H NMR (300 MHz, DMS0-D6) 5 ppm 3 10 (s, 3 H) 3 37 (s, 3 H) 5 71 (dd, J=7 72, 2 21 Hz, 1 H) 7 44 (dd, J=8 82, 2 21 Hz, 1 H) 7 75 (s, 1 H) 7 78 (d, J=l 84 Hz, 1 H) 7 88 (m, 3 H) 7 98 (d, J=3 31 Hz, 1 H) 8 01 (d, J=3 68 Hz, 1 H) 8 15 (s, 1 H) 10 09 (s, 1 H) 11 51 (d, J=2 21 Hz, 1 H) MS (ESI-) mz 504 1 (M-H) [00774]Example 37 Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yI)-2-methoxy-3-(perfIuoroethyl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2.60) (Formula Removed) [00775]Part N Preparation of l-methoxy-4-nitr0-2-(perfluoroethyl)benzene [00776] To a 250mL round-bottom flask was added 2-brom0-l-methoxy-4-nitrobenzene (3 5g, 15 08mmol), copper(I) iodide (5 75g, 30 2mmot), and sodium 2,2,3,3,3-pentafluoropropanoate (5 25g, 28 2mmoI) in DMF (75ml) and toluene (25ml) to give a tan suspension The mixture was heated at 150°C and toluene was removed by a Dean-Stark trap The mixture was heated at 155°C for 6h under nitr0gen, cooled and poured into 100mL of water and 100mL of ether, filtered through a 1-inch plug of Celite and the plug was rinsed with ether The filtrate layers were separated The organic layer was washed with brine, dried (Na2SO4) filtered and concentrated The dark oil was flash chromat0graphed on an isco 40g silica cartridge eluting with 4 1 hexaneEtONc to give a yellow oil that was a (3 1) mix of desired material and starting material (1 Sg, 37%) [00777] Part B Preparation of 4-nitr0-2-(perfluoroethyl)phenol [00778] In a 100mL round-bottom flask was added the product from Part N (1 4g, 5 16mmol) and pyridine hydrochloride (4g, 34 6mmol) neat The mixture was heated at 210°C for 20min, cooled, and partitioned between EtONc and water The organic layer was washed with brine, dried (Na2SO4) and concentrated The crude product was flash chromat0graphed on an Isco 12g silica cartridge eluting with 3 2 hecxaneEtONc to give a yellow oil (1 3g, 98%) [00779] Part C Preparation of 2-iod0-4-nitr0-6-(perfluoroethyl)phenol [00780] In a 100mL round-bottom flask was added the product from Part B (1 3g, 5 06mmol) and N- lodosuccmimide (1 251 g, 5 56mmol) in acetonitrile (16 85ml) to give a yellow solution The solution was stirred for 16h, diluted with 100mL EtONc and washed 2 x 50ml with 10% sodium thiosulfate, brine, dried (Na2SO4) and concentrated to an orange semisolid The semisolid was flash chromat0graphed on an Isco 40g silica cartridge eluting with 3 1 hexane EtONc to give a deep yelloworange oil (1 3g, 67%) [00781] Part D Preparation of 1 -iod0-2-methoxy-5-nitr0-3-(perfIuoroethyl)benzene [00782] In a 100mL round-bottom flask was added the product from Part C (1 04g, 2 72mmol) potassium carbonate (0 563g, 4 07mmol) and dimethyl sulfate (0 41 Ig, 3 26mmol) in acetone (20ml) to give a brown suspension The mixture was heated at gentle reflux for 16h, cooled, diluted into EtONc, washed with water and brine The organic layer was dried Na2SO4, filtered and concentrated to a yellow oil that was punfied by flash chromat0graphy on an Isco 40g silica cartridge eluting with 9 1 hexaneEtONc (600mg, 56%) [00783] Part E Preparation of 3-iod0-4-methoxy-5-(perfluoroethyl)aniline [00784] In a 250mL round-bottom flask was added the product from Part D (0 6g, 1 51 Immol), iron (0 422g, 7 56mmol), and ammonium chloride (0 121g, 2 267mmol) m a solvent mix of EtOH (9ml), THE (9ml) and water (3ml) to give a brown suspension that was heated at 95-100°C for 2h The reaction mix was filtered through a plug of Celite and the Celite was rinsed repeatedly with EtOH The filtrate was concentrated and the residue was dissolved in EtONc, washed with water, bnne, dried (Na2SO4), filtered and concentrated to give an oil (560mg, 99%) [00785] Part F Preparation of 1,5-diiod0-2-methoxy-3-(perfluoroethyl)benzene [00786] In a 25mL round-bottom flask under nitr0gen was added the product from Part E (0 565g, 1 539mmol), tert-butyl nitrite (0 293ml, 2 463mmol), copper(I) iodide (0 293g, 1 539mmol), sodium iodide (0 231g, 1 539mmol) and iodine (0 195g, 0 770mmol) in DME (15 39ml) to give a brown suspension The mixture was heated at 60°C for 3h, cooled and filtered through Celite washing the Celite pad well with EtONc The EtONc filtrate was treated with 10% sodium thiosulfate, brine, dried (Na2SO4), filtered and concentrated to a dark oil The crude material was purified by flash chromat0graphy on an Isco 40g silica cartridge eiuting with 95 5 hexaneEtONc to give a yellow oil (360mg, 49%) [00787]Part G Preparation of l-(3-iod0-4-methoxy-5-(perfluoroethyl)phenyl)pyrimidine-2,4(lH,3H)-dione [00788] In a 20mL microwave tube was added the product fi-om Part F (0 36g, 0 753mmol), IH-pyrimidine-2,4-dione (0 lOlg, 0 904mmol), potassium phosphate tnbasic (0 336g, 1 582mmol) N-(2-cyanophenyl)picolinamide (0 034g, 0 islmmol) and copper(I) iodide (0 014g, 0 075mmol in DMSO (7ml) The vessel was sealed and the mixture was sparged with N2 for 30min, heated at 60°C for 24h, cooled and diluted into EtONc The EtONc layer was washed with IM HCl, saturated NaHC03, and saturated NaCl, dried (Na2SO4), filtered and concentrated The residue was flash chromat0graphed on an Isco 40g silica cartridge eluting with hexane --y 1 1 hexaneEtONc to give a yellow foam (100mg, 29%) [00789]Part H Preparation of N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-3-(perfluoroethyl)pheny])naphthalen-2-yl)methanesulfonamide [00790] In a 5mL microwave tube were combined the product from Part G (0 l0g, 0 216mmol), Example 2N, Part B (0 075g, 0 216mmol), and potassium phosphate tribasic (0 096g, 0 454mmol) in 3 1 tetrahydrofuran-water (5mL) and degassed by nitr0gen sparge for 10min The mixture was then treated with PN-Ph (CNS 97739-46-3) (1 898mg, 6 49moI) and tris(dibenzylideneacetone)dipalladium(O) (1 982mg, 2 164nmol) followed by degassing for another 5min The flask was then sealed and stirred at 50°C for 16h and partitioned between EtONc and water The EtONc layer was vashed with 0 IM HCl, saturated NaHCOs, and saturated NaCl The organic was dned Na2SO4, stirred for 0 5h with 3-mercapt0-propyl functionalized silica to remove metals, filtered and concentrated The crude product was purified by chromat0graphy on an Isco 12g silica cartridge eluting with CH2CI2 ~y 3% MeOH m CH2CI2 to give a light yellow foam (84mg, 99%) m p I62-165°C H NMR (300 MHz, DMS0-D6) 5 ppm 3 10 (s, 3 H) 3 33 (s, 3 H) 5 70 (d, J=7 72 Hz, 1 H) 7 44 (dd, J=8 82, 2 21 Hz, 1 H) 7 70 - 7 76 (m, 2 H) 7 80 (d, J=2 57 Hz, 1 H) 7 86 (d, J=8 09 Hz, 1 H) 7 91 (d, J=2 57 Hz, 1 H) 8 00 (dd, J=8 82, 2 94 Hz, 2 H) 8 12 (s, I H) 10 10 (s, 1 H) 11 50 (s, 1 H) MS (ESI-) ?nz 554 (M-H) [00791]Example 38 Preparation of (E)-N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxy-3-(thiophen-2-yl)phenyl)-2,3-dihydr0-lH-mden-l-yhdene)methanesuIfonohydrazide (compound IB-L0- 2 51) (Formula Removed) [00792] Part N Preparation of l-(3-brom0-4-methoxy-5-(l-ox0-2,3-dihydr0-lH-inden-5-yl)phenyl)- pyrimidine-2,4( 1 H,3H)-dione [00793] In a 100mL round-bottom flask was added the product from Example 18, Part C (846mg, 2 00mmol), Example 4, Part N (516mg, 2 O00mmol), potassium phosphate (892mg, 4 20mmol), PN-Ph (CNS 97739-46-3) (17 54mg, 0 060mmol) and tns(dibenzylideneacetone)-dipalladium(O) (18 31mg, 0 020mmol) m THF (12 0ml) and water (4 0ml) The vessel was sealed and the mixture was sparged with nitr0gen for 5min and stirred at ambient temperature for 72h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bic£irbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered through celite and evaporated The residue was punfied with silica gel eluting with 1 to 4% methanol in CH2CI2 to give a solid (690mg, 81%) [00794] Part B Preparation of (E)-N-(5-(3-brom0-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxyphenyl)-2,3-dihydr0-lH-inden-l-ylidene)methanesulfonohydrazide [00795] In a 50mL round-bottom flask was added the product from Part N (685mg, 1 603mmol) and methanesulfonohydrazide (194mg, 1 764mmol) in MeOH (20ml) The mixture was warmed to 40C and stirred for 24h The mixture was cooled, filtered and washed with methanol to give a solid (569mg, 68%) [00796]Part C Preparation of (E)-N-(6-(5-(2,4-diox0-3,4-dihydropyrimidm-l(2H)-yI)-2-methoxy-3- (thiophen-2-yl)phenyl)-2,3-dihydr0-lH-inden-l-ylidene)methanesulfonohydrazide [00797] In a 5mL microwave tube was added the product from Part B (52mg, 0 1 00mmol), thiophen-2- y1boronic acid (12 81mg, 0 1 00mmol), 1, r-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3 26mg, 5 Olfimol) and potassium phosphate (42 5mg, 0 200mmol) in THF (3 0ml) and water (1 0ml) The mixture was sparged by nitr0gen for 5min and heated at SOC for 3h The mixture was partitioned with ethyl acetate and 1M HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was freated with 3-mercaptopropyl functionalized silica gel, filtered through celite and evaporated The residue was purified by reverse phase chromat0graphy NN method to give a white solid (27mg, 52%) H NMR (300 MHz, DMS0-D6) 5 ppm 2 86 (m, 2 H) 3 09 (s, 3 H) 3 14 (m, 2 H) 3 32 (s 3 H) 5 69 (d, J=7 72 Hz, 1 H) 7 18 (dd, J=5 15, 3 68 Hz, 1 H) 7 41 (d, J=2 57 Hz, 1 H) 7 63 (m, 3 H) 7 75 (m, 2 H) 7 86 (d, J=8 09 Hz, 1 H) 7 91 (d, J=2 94 Hz, 1 H) 9 96 (s, 1 H) 11 48 (s, 1 H) MS (ESI+) mz 523 (M+H) [00798]Example 39 Preparation of (E)-N-(6-(5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-3-(furan-2-yl)-2-methoxyphenyl)-2,3 -dihydr0-1 H-inden-1 -ylidene)methanesulfonohydrazide (compound IB-L0- 2 55) (Formula Removed) [00799] In a 5ml microwave tube was added the product from Example 38, Part B (52mg, 0 100mmol), furan-2-y1boronic acid (11 20mg, 0 100mmol), l,r-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3 26mg, 5 Oljimol) and potassium phosphate (42 5mg, 0 200mmol) in THF (3 0ml) and water (1 0ml) The mixture was sparged by nitr0gen for 5min and heated at 50C for 3h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyI functionalized silica gel, filtered through celite and evaporated The residue was purified by reverse phase chromat0graphy NN method to give a solid (24mg, 47%) H NMR (300 MHz, DMS0-D6) S ppm 2 86 (m, 2 H) 3 09 (s, 3 H) 3 14 (m, 2 H) 3 36 (s, 3 H) 5 68 (d, J=8 09 Hz, 1 H) 6 69 (dd, J=3 31, I 84 Hz, 1 H) 7 09 (d, J=3 31 Hz, 1 H) 7 41 (d, J=2 57 Hz, 1 H) 7 62 (m, 2 H) 7 75 (d, J=8 09 Hz! 1 H) 7 80 (d, J=2 57 Hz, 1 H) 7 86 (m, 2 H) 9 97 (s, 1 H) 11 46 (s, 1 H) MS (ESI+) mz 507 (M+H) [00800]Example 40 Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-ethoxyphenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 23) (Formula Removed) {00801] Part N Preparation of 2-tert-butyl-4-iodophenol [00802] To a 250mL round-bottom flask was added 2-tert-butylphenol (3 76g, 25mmol) in MeOH (50 0ml) to give a colorless solution Sodium hydroxide (1 200g, 30 0mmol) was added and the mix was stirred until the hydroxide was completely dissolved The solution was cooled to 0°C and treated with sodium iodide (1 75g, 11 6mmol) followed by dropwise addition of 10% sodium hypochlorite solution (7 2ml, 11 6mmo]) The addition of sodium iodide followed by sodium hypochlorite was repeated twice and the mixture was stirred at 0°C for 30mm The mixture was treated with 10% ww solution of sodium thiosulfate, stirred for 30min and treated with concentrated HCl dropwise to a constant pH of 1 The mixture was extracted 3X with EtONc The extracts were combined, washed with brine, dried (MgSO4), filtered and concentrated The crude oil was flash chromat0graphed on an isCO 80g silica cartndge eluting with hexane ~y 4 1 hexaneEtONc to give a yellow oil (5 2g , 75%) [ 00803] Part B Preparation of 2-brora0-6-tert-butyl-4-iodophenol [00804] To a 250mL round-bottom flask was added the product from Part N (4 8g, 17 38mmol) and 1,3- dibrom0-5,5-dimethylhydantoin (2 61g, 9 13mmol) in chloroform (87ml) to give an orange solution The reaction mixture was stirred for 2h resulting in a black solution that was washed with water, brine, dried (Na2SO4) and concentrated The black oil was flash chromat0graphed on a 120g Isco silica cartridge elutmg with hexane to give a pinkish solid (4 84g, 78%) [00805]Part C Preparation of 1 -brom0-3-tert-butyl-2-ethoxy-5-iodobenzene [00806] To a S0ml round-bottom flask was added the product from Part B (888mg, 2 5mmoI), ethyl iodide (409mg, 2 63mmol), and potassium carbonate (415mg, 3 00mmol) in acetone (12ml) to give a green suspension The mixture was heated at reflux for 16h, cooled and concentrated The residue was partitioned between water and EtONc The organic layer was washed twice with brine, dned over Na2SO4, filtered and concentrated to a red oil The oil was flash chromat0graphed on an Isco 40g silica cartridge eluting with hexane to give a clear oil (820mg, 86%) [00807]Part D Preparation of 1 -(3-brom0-5-tert-butyl-4-ethoxyphenyl)pyrimidine-2,4(lH,3Hydione [0080S] In a 20mL microwave tube under nitr0gen flush was added the product from Part C (0 4g 1 044mmol), lH-Pyrimidine-2,4-dione (0 140g, 1 253mmol), and potassium phosphate tribasic (0 465g, 2 193mmol) in DMSO (5ml) to give a colorless suspension N-(2-cyanophenyl)picolinamide (0 047g, 0 209mmol) was added and the mix was sparged with nitr0gen for 10min Copper(l) iodide (0 020g, 0 104mmol) was added and the mix was sparged once again for 10min, placed under nitr0gen and heated at 60°C for 18h The mixture was cooled and partitioned between EtONc and water adjusting the pH to 1 with HCl The aqueous layer was extracted 2X with EtONc The orgamcs were combined, washed with water, saturated NaHCOs, and saturated NaCl The organic layer was dried (Na2SO4), stirred with 3- mercaptopropyl fianctionalized silica for Ih, filtered and concentrated The crude product was purified by chromat0graphy on an isCO 12g silica cartridge eluting with 2% MeOH in CH2CI2 to give a white powder (266mg, 69%) 100809]Part E Preparation of N-(6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-ethoxyphenyl)naphthalen-2-yl)methanesulfonamide [00810] In a 5mL microwave tube was added the product from Part D (55 Img, 0 15mmol), the product from Example 2N, Part B (52 Img, 0 150mmol), potassium phosphate tribasic (63 7mg, 0 300mmol) and l,r-bis(di-tert-butylphosphino)ferrocene palladium dichlonde (4 89mg, 7 SOjimol) in THF (3ml) water (1ml) The mixture was sparged for 10min with nitr0gen, heated sealed at 50°C for 4h, cooled and diluted into EtONc The EtONc layer was washed with 1M HCl, saturated NaHCOa, saturated NaCl, dried (Na2SO4) and treated simultaneously with mercaptopropyl silica gel, filtered and concentrated The residue was flash chromat0graphed on a 12g Isco silica cartridge eluting with 2% MeOH in CH2CI2 to give a solid, (16mg, 21%) m p 196-202°C H NMR (300 MHz, DMS0-D6) 8 ppm 1 00 (t, J=6 99 Hz, 3 H) 1 44 (s, 9 H) 3 09 (s, 3 H) 3 43 (q, J=7 11 Hz, 2 H) 5 64 (dd, J=7 91, 1 29 Hz, 1 H) 7 32 (d, J=2 94 Hz, 1 H) 7 36 (d, J=2 94 Hz, 1 H) 7 41 (dd, J=8 82, 2 21 Hz, 1 H) 7 72 (s, 1 H) 7 74 (d, J=l 47 Hz, 1 H) 7 80 (d, J=7 72 Hz, 1 H) 7 90 - 8 00 (m, 2 H) 8 05 (s, 1 H) 10 04 (s, 1 H) 11 41 (s, 1 H) MS (ES1-) mz 506 (M-H) [00811]Example 41 Preparation of N-(6-(3-tert-butyl-2-chlor0-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)phenyl)naphthalen-2-yl)methanesulfonamide (compound IB-L0-2 14) (Formula Removed) [00812] Part N Preparation of 2-brom0-6-tert-butyl-4-iodoaniline [00813] In a 50mL round-bottom flask was added 2-brom0-6-tert-butylaniline [prepared by the method of Onitsuka, et al Organometallics, 25(5), 2006, pp 1270-1278] (1 18g, 5 17mmol) and sodium bicarbonate (0 782g, 9 31mmol) in water (5ml) The mixture was cooled m an ice bath and iodine (1 444g, 5 69mmol) was added in several portions The mixture was wanned to ambient temperature and stirred for 16h The mixture was treated with aqueous sodium thiosulfate, extracted by ethyl acetate, dried with sodium sulfate, fihered and evaporated The residue was purified on silica gel eluting with 5% ethyl acetate in hexane to give an oil (1 2g, 65%) [00814] Part B Preparation of 1 -brom0-3-tert-butyl-2-chlor0-5-iodobenzene [00815]To a mixture of tert-butyl nitrite (0 198ml, 1 5mmol) and copper(II) chloride (161mg, 1 2mmol) in acetonitrile (5mL) was added the product from Part N (354mg, 1 0mmol) as a solution in acetonitrile (5mL) The mixture was heated at 60C for 30min, cooled, partitioned with ethyl acetate and IM HCl The organic layer was washed with bnne, dried with sodium sulfate, filtered and evaporated The residue was purified on silica gel eluting with 5% ethyl acetate in hexane to give the product (300mg, 81%) [008I6|Part C Preparation of l-(3-brom0-5-tert-butyl-4-chlorophenyl)pyrimidme-2,4(lH,3H)-dione [00817] In a 20mL microwave tube was added the product from Part B (300mg, 0 803mmol), pyrimidine-2,4(lH,3H)-dione (99mg, 0 884mmol), N-(2-cyanophenyl)picolinamide (35 9mg, 0 161mmol), copper(I) iodide (15 30mg, 0 050mmol) and potassium phosphate (358mg, 1 687mmol) in DMSO (5ml) The mixture was sealed, purged with nitr0gen and heated at 600 for 4h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dned with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was purified on silica gel eluting with 10% to 40%i ethyl acetate in hexane to give a solid (175mg, 61%) [00818]Part D Preparation of N-(6-(3-tert-butyl-2-chlor0-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)- yl)phenyl)naphthalen-2-yl)methanesulfonamide [00819] In a 5mL microwave tube was added the product from Part C (35 8mg, 0 10mmol), the product from Example2N, Part B (38 2mg, 0 l10mmol), l,r-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3 26mg, 5 OOnmol) and potassium phosphate (42 5mg, 0 200mmol) in THFWater (3ml 1ml) The mixture was purged with nitr0gen for 5min and heated at 60C for 2h The mixture was partitioned with ethyl acetate and IM HCl The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered and evaporated The residue was purified on silica gel elutmg with 1 lethyl acetatehexane to give a solid that was triturated with 1% methanol in CH2CI2 to give a white solid (29mg, 55%), melting point y 280C H NMR (300 MHz, DMS0-D6) 6 ppm 1 53 (s, 9 H) 3 08 (s, 3 H) 5 69 (d, J=7 72 Hz, 1 H) 7 42 (m, 2 H) 7 52 (dd, J=8 46, 1 84 Hz, 1 H) 7 56 (d, J=2 57 Hz, 1 H) 7 74 (d, J=l 84 Hz, 1 H) 7 84 (d, J=7 72 Hz, 1 H) 7 88 (s, 1 H) 7 91 (d, J=8 82 Hz, 1 H) 7 95 (d, J=9 19 Hz, 1 H) 10 04 (s, 1 H) 11 46 (s, 1 H) MS (ESI-) mz 496 (M-H) [00820]Example 42 Preparation of N-((6-(3-re?Nbutyl-5-(2,4-diox0-3,4-dihydropynmidin-l(2H)-yl)-2-methoxyphenyl)benzo[c]isoxazol-3-yl)methyl)methanesulfonamide (compound IB-L0-l 45) (Formula Removed) [00821]Part N Preparation of N-((6-bromobenzo[tf]isoxazol-3-yl)methyl)-N-(4-methoxybenzyl)-methanesulfonamide [00822] To a refluxing solution of 6-brom0-3-methy1benzo[d]isoxazole (1 0g, 4 72mmol) in CCI4 (25ml) was added l-bromopyrrolidine-2,5-dione (0 923g, 5 19mmol) and benzoic peroxyanhydnde (0 114g, 0 472mmol) The mixture was refluxed for 6h, and then cooled to room temperature, filtered thru celite, and concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using CH2CI2 as the eluent to give the dibr0mlde as a solid (0 84g, 43%) To a solution of the dibr0mlde (0 20g, 0 687mmol) and N-(4-methoxybenzyl)methanesulfonamide (0 148g, 0 687mmol) in EtOH (3ml) was added IN aq NaOH (0 722ml, 0 722mmol), and the resulting mixture was stirred at 80°C for 90min The mixture was partitioned between 0 IN aq HCL (10mL) and EtONc (2 x 10mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using 2 3 EtONc hexanes as eluent to give the title compound as an oil (65mg, 22%) [00823]PartB Preparation of jV-(4-methoxybenzyl)-jV-((6-(4,4,5,5-tetramethyl-l 3,2-dioxaborolan-2- yl)benzo[£f]isoxazol-3-yl)methyl)methanesulfonamide [00824] N solution of the product from Part N (56mg, 0 132mmol), bis(pinacolato)diboron (37mg, 0 145mmol), and potassium acetate (39mg, 0 395mmol) in 1,4-dioxane (1 3mL) was degassed by bubbling with N2 gas for 15min l,r-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (3mg, 0 004mmol) was added and the resulting mixture was stirred at 80°C for 16h, filtered and concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using 1 2 EtONc hexanes as the eluent to give the title compound as a colorless oil (49mg, 79%) |00825]Part C Preparation of iV-((6-(3-?er?-butyl-5-(2,4-dio\0-3,4-dihydropyrimidin-l(2H)-yl)-2- methoxyphenyl)benzo[cr]isoxazol-3-yl)methyl)-N-(4-methoxybenzyl)methanesulfonamide [00826] N mixture of the product from Example C (31 8mg, 0 079mmol), the product from Part B (45mg, 0 095mmol) in EtOH (0 5mL), toluene (0 5mL) IM aq NSLJCOI (0 095mL, 0 095mmol) was degassed by bubbling with N2 gas for 10min 1,1- Bis(diphenylphosphino)ferrocene-palladium(II) dichlonde dichloromethane complex (2mg, 2 4|imol) was added, and degassing with N2 was continued for 5min The reaction mixture was sealed and heated at IO0°C in a microwave reactor for 1 h The mixture was concentrated in vacuo, and the crude product was purified by column chromat0graphy on silica gel using 1 9 MeOH CHCI3 as the eluent The ttle compound was obtained as a light brown solid (41mg. 83%) [008271Part D Preparation of Nf-((6-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2Hf)-yl)-2- methoxyphenyl)benzo[£]isoxazol-3-yl)methyl)methanesulfonamide [00828] N solution of the product from Part C (39mg, 0 063mmol) in TFN (0 5mL) was stirred at 40°C for 6h TFN was removed in vacuo and the crude product was purified by column chromat0graphy on silica gel using 4% MeOH in CHCI3 as the eluent to give the title compound (13mg, 41%) H NMR (300 MHz, CDCI3) S 8 39 (s, 1 H) 7 74 - 7 82 (m, 2 H) 7 57 (dd, J=S 27, 1 65 Hz, 1 H) 7 36 (d, y=7 72 Hz, 1 H) 7 25 (d, J=2 57 Hz, 1 H) 7 19 (d, J=2 94 Hz, 1 H) 5 82 (dd, J=7 72, 2 21 Hz, 1 H) 5 25 - 5 33 (m, 1 H) 4 70 (d, J=6 25 Hz, 2 H) 3 29 (s, 3 H) 3 12 (s, 3 H) 1 45 (s, 9 H) [00829] Example 43 Preparation of methyl 2-(5-(3-tert-butyl-5-(2,4-diox0-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)-2,3-dihydr0-17-inden-l-yIidene)hydrazinecarboxylate (compound IB-L0-2.24) (Formula Removed) TSiNHCOjCHj [00830] To a solution of the product from Example 4, Part B (0 05g, 0 124mmol) in MeOH (1ml) was added methyl carbazate (17mg, 0 185mmol) The mixture was stirred at 60°C for 16h, and then concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using 5% MeOH in CH2CI2 as the eluent to give the title compound (44mg, 74%) H NMR (300 MHz, DMS0-de) 5 11 40 (s, 1 H) 10 05 (s, 1 H) 7 78 (d,y=8 09 Hz, 1 H) 7 69 (d,7 72 Hz, 1 H) 7 45 - 7 57 (m, 2 H) 7 24 - 7 33 (m, 2 H) 5 64 (d, J=8 09 Hz, 1 H) 3 71 (s, 3 H) 3 28 (s, 3 H) 3 06 - 3 16 (m, 2 H) 2 78 - 2 88 (m, 2 H) 1 40 (s, 9 H) [00831]Example 44 Preparation of l-(3-Ze7-butyl-4-methoxy-5-(l-oxoisoindolin-5-yl)phenyl)-pyrimidine-2,4(IH,3H)-dione (compound IB-L0-2 30) (Formula Removed) [00832] Part N Preparation of 5-brom0-2-(2,4-dimethoxybenzyl)isoindolin-1 -one [00833] To a solution of methyl 4-brom0-2-(bromomethyl)benzoate (1 0g, 3 25mmol) and (2,4- dimethoxyphenyl)methanamme (0 65g, 3 90mmol) m THF (16mL) was added triethylamine (0 91mL, 6 Smmol), and the resulting mixture was stirred at room temeprature for 16h The resulting solid was filtered off, and the filtrate was concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using 1 4 EtONc hexanes as the eluent to give the title compound as a colorless solid (0 52g, 44%) [00834]Part B Preparation of 2-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)isoindolin-l-one [00835] The product from Part N (100mg, 0 276mmol) was subjected to the conditions described for Example 42, Part B to give the title compound as an oil (107mg 95%) (00836]Part C Preparation of 1 -(3-rerr-butyl-5-(2-(2,4-dimethoxybenzyl)-l-oxoisoindolin-5-yl)-4- methoxyphenyl)pyrimidme-2,4( 1 H,3f)-dione [00837] The product from Part C (44mg, 0 11 Immol) was subjected to the conditions described for Example 42, Part C to give the title compound (50mg, 81%) [00838]Part D Preparation of 1 -(3-te-?-butyl-4-methoxy-5-( 1 -oxoisoindolin-5-yl)phenyl) pyrimidine- 2,4(1H,3H)-dione [00839] N solution of the product from Part C (48mg, 0 086mmol) in CH2CI2 (0 3ml) and TFN (0 6ml, 7 79mmol) was stirred at room temperature for 16h, and then concentrated in vacuo The crude product was purified by column chromat0graphy on silica gel using 5% MeOH in CHCI3 as the eluent to give the title compound as a colorless solid (22mg, 63%) H NMR (300 MHz, DMS0-de) 6 11 41 (d, J=\ 84 Hz, 1 H) 8 61 (s, 1 H) 7 72 - 7 83 (m, 3 H) 7 62 - 7 69 (m, 1 H) 7 29 - 7 36 (m, 2 H) 5 65 (dd, J=8 09, 2 21 Hz, 1 H) 4 44 (s, 2 H) 3 25 (s, 3 H) 1 41 (s, 9 H) [00840]Example 45 Preparation of N-(2-(6-(3- 0 0luM, C -- luM > IC50 > 0 luM, and D -- IC50 > luM, ND - not determined TablelC (Table Removed) [001129] HCV Polymerase Replicon Nssay [001130] Two stable subgen0mlc replicon cell lines were used for compound characterization in cell culture one derived from genotype la-H77 and one derived from genotype 1b-Con 1 (obtained from Npath, LLC, St Louis, MO) Nll replicon constructs were bicistronic subgen0mlc replicons similar to those described by Bartenschlager and coworkers (Lohmann et al, Replication of Subgen0mlc Hepatitis C Virus RNNs m a Hepatoma Cell Line, SCIENCE 285 110-3(1999)) The genotype la replicon construct contains NS3-NS5B coding region derived from the H77 strain of HCV (la-H77) (Blight et al, Efficient Replication of Hepatitis C Virus Genotype la RNNs in Cell Culture, J VlROL 77 3181-90 (2003)) The replicon also has a firefly luciferase reporter and a neomycin phosphotransferase (Neo) selectable marker These two coding regions, separated by the FMDV 2a protease, comprise the first cistron of the bicistronic replicon construct, with the second cistron containing the NS3-NS5B coding region with addition of adaptive mutations E1202G, K1691R, K2040R and S2204I The 1 b-Con 1 replicon construct is identical to the la-H77 replicon, except that the NS3-NS5B coding region was derived from the Ib-Conl strain, and the adaptive mutations are E1202G, T1280I and S2204I Replicon cell lines were maintained m Du1becco's modified Eagles medium (DMEM) containing 10% (vv) fetal bovine serum (FBS), 100 lUml penicillin, 100mgml streptomycin (Invitr0gen), and 200mgml G418 (Invitr0gen) [001131] The inhibitory effects of compounds on HCV replication were determined by measuring activity of the luciferase reporter gene Briefly, replicon-containing cells were seeded into 96 well plates at a density of 5000 cells per well in 100ul DMEM containing 5% FBS 16-24h later, the compounds were diluted in dimethyl sulfoxide (DMSO) to generate a 200x stock in a series of eight half-l0g dilutions The dilution series was then further diluted 100-fold in the medium containing 5% FBS Medium with the inhibitor was added to the overnight cell culture plates already containing 100ul of DMEM with 5% FBS In assays measuring inhibitory activity in the presence of human plasma, the medium from the overnight cell culture plates was replaced with DMEM containing 40% human plasma and 5% FBS The cells were incubated for three days in the tissue culture incubators and were then lysed for RNN extraction For the luciferase assay, 30ul of Passive Lysis buffer (Promega) was added to each well, and then the plates were incubated for 15min with rocking to lyse the cells Lucifenn solution (50 to l00ul, Promega) was added to each well, and luciferase activity was measured with a Victor II luminometer (Perkm-Elmer) The percent inhibition of HCV RNN replication was calculated for each compound concentration and the EC50 value was calculated using nonlinear regression curve fitting to the 4-parameter l0gistic equation and GraphPad Prism 4 software [001132] When tested by the above method, the compounds of this invention inhibit HCV polymerase lN andor IB The legend in the table below is as follows N - EC50 < 0 0luM, B - 0 luM > EC50 > 0 01uM, C -- luM > EC50 > 0 luM, and D -- EC50 > luM, ND - not determined Table EC. (Table Removed) [001133] Nll references (patent and non-patent) cited above are incorporated by reference into this patent application The discussion of those references is intended merely to summarize the assertions made by their authors No admission is made that any reference (or a portion of ay reference) is relevant prior art (or prior art at all) Npplicants reserve the right to challenge the accuracy and pertinence of the cited references WE CLAIM: 1. A compound or salt thereof, wherein: the compound corresponds in structure to formula I-LO: (Formula Removed) ---- is selected from the group consisting of single carbon-carbon bond and double carbon-carbon bond; R1 is selected from the group consisting of hydrogen, methyl, and nitrogen-protecting group; R2 is selected from the group consisting of hydrogen, halo, hydroxy, methyl, cyclopropyl, and cyclobutyl; R3 is selected from the group consisting of hydrogen, halo, oxo, and methyl; R4 is selected from the group consisting of halo, alkyl, alkenyl, alkynyl, nitro, cyano, azido, alkyloxy, alkenyloxy, alkynyloxy, amino, aminocarbonyl, aminosulfonyl, alkylsulfonyl, carbocyclyl, and heterocyclyl, wherein: (a) the amino, aminocarbonyl, and aminosulfonyl optionally are substituted with: (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, and alkylsulfonyl, or (2) two substituents that, together with the amino nitrogen, form a single-ring heterocyclyl, and (b) the alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, and alkylsulfonyl, optionally are substituted with one or more substituents independently selected from the group consisting of halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein: the amino optionally is substituted with: (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, together with the amino nitrogen, form a single- ring heterocyclyl, and (c) the carbocyclyl and heterocyclyl optionally are substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, oxo, nitro, cyano, azido, hydroxy, amino, alkyloxy, trimethylsilyl, carbocyclyl, and heterocyclyl, wherein: the amino optionally is substituted with: (1) one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylcarbonyl, alkylsulfonyl, alkyloxycarbonyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, and heterocyclylalkyl, or (2) two substituents that, together with the amino nitrogen, form a single-ring heterocyclyl; R5 is selected from the group consisting of hydrogen, hydroxy, alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, carbocyclylsulfonyloxy, haloalkylsulfonyloxy, and halo; R6 is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of RE, RF, RG, RH, R1, RJ, and RK; each RE is independently selected from the group consisting of halo, nitro, hydroxy, oxo, carboxy, cyano, amino, imino, azido, and aldehydo, wherein: the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl; each RF is independently selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein: each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, imino, nitro, azido, oxo, aminosulfonyl, alkylsulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein: the amino, imino, aminosulfonyl, aminocarbonyl, carbocyclyl, and heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, alkylsulfonylamino, hydroxy, and alkyloxy, wherein: amino portion of the alkylsulfonylamino optionally is substituted with a substituent selected from the group consisting of alkyl, alkenyl, and alkynyl; each RG is independently selected from the group consisting of carbocyclyl and heterocyclyl, wherein: each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenyicarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein: the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl; each RH is independently selected from the group consisting of alkyloxy, alkenyloxy, alkynyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, and alkynylsulfonyloxy, wherein: each such substituent optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, 0X0, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenyicarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein: the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl; each R1 is independently selected from the group consisting of alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, aminocarbonyl, alkyloxycarbonyl, carbocyclylcarbonyl, and heterocyclylcarbonyl, wherein: (a) the alkylcarbonyl, alkenylcarbonyl, and alkynylcarbonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylcarbonyloxy, alkenyicarbonyloxy, alkynylcarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, and (b) the aminocarbonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxyalkyl, carbocyclyl, heterocyclyl, alkylsulfonyl, and alkylsulfonylamino, wherein: the carbocyclyl and heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of halo, alkyl, and oxo; each RJ is independently selected from the group consisting of carbocyclylsulfonylamino, heterocyclylsulfonylamino, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, alkyloxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylamino, alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, aminocarbonylamino, alkyloxycarbonylaminoimino, alkylsulfonylaminoimino, alkenylsulfonylaminoimino, and alkynylsulfonylaminoimino, wherein: (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyl, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkenyl, alkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein: (1) the carbocyclyl portion of the carbocyclylalkyl and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or more substituents independently selected from the group consisting of carboxy, halo, 0X0, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein: the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkyloxy, alkenyloxy, and alkynyloxy, wherein: the alkyl optionally is substituted with one or more hydroxy; (c) the carbocyclyl and heterocyclyl portions of such substituents optionally are substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkyloxy, alkenyloxy, alkynyloxy, halo, nitro, cyano, azido, and amino, wherein: the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl; and each RK is independently selected from the group consisting of aminosulfonyl, alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl, wherein: (a) the alkylsulfonyl, alkenylsulfonyl, and alkynylsulfonyl optionally are substituted with one or more substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitre, azido, oxo, aminosulfonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aikylcarbonyloxy, alkenylcarbonyloxy, alkynyicarbonyloxy, alkyloxy, alkenyloxy, alkynyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl, wherein: the amino, aminosulfonyl, and aminocarbonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl; and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl. 2. The compound or sah of claim 1, wherein: R1 is selected from the group consisting of hydrogen and methyl; R2 is selected from the group consisting of hydrogen and halo; R3 is selected from the group consisting of hydrogen and halo; R4 is selected from the group consisting of C1-C4-alkyl, C3-C6-carbocyclyl, and 5-6-membered heterocyclyl, wherein: (a) the C1-C4-alkyl optionally is substituted with up to three substituents independently selected from the group consisting of halo, oxo, hydroxy, alkyloxy, and trimethylsilyl, and (b) the C3-C6-carbocyclyl and 5-6-membered heterocyclyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, halo, and alkylsulfonylamino; R5 is selected from the group consisting of hydrogen, hydroxy, alkyloxy, and halo; R6 is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent is substituted with one, two, three substituents independently selected from the group consisting of RE, RF, RG, RH, R1 RJ and RK; each R is independently selected from the group consisting of chloro, fluoro, nitro, hydroxy, oxo, carboxy, amino, imino, aldehydo, and alkylamino; each RF is an independently selected alkyl optionally substituted with a substituent selected from the group consisting of carboxy, halo, amino, imino, and aminosulfonyl, wherein: the amino, imino, and aminosulfonyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, alkylsulfonyl, and alkylsulfonylamino; each R is independently selected from the group consisting of alkylcarbonyl and aminocarbonyl. wherein: the aminocarbonyl optionally is substituted with a substituent selected from the group consisting of alkyl, alkyloxyalkyl, alkylsulfonyl, and alkylsulfonylamino; each RJ is independently selected from the group consisting of alkylsulfonylamino, alkenylsulfonylamino, alkynylsulfonylamino, and alkylsulfonylaminoimino, wherein: (a) the amino portion of such substituents optionally is substituted with a substituent independently selected from the group consisting of carbocyclylalkyi, heterocyclylalkyl, alkylcarbonyloxy, aminocarbonylalkyl, alkyl, alkylcarbonyl, alkyloxycarbonyl, alkyloxyalkyloxycarbonyl, alkylcarbonyloxyalkyl, and alkylsulfonyl, wherein: (1) the carbocyclyl portion of the carbocyclylalkyi and the heterocyclyl portion of the heterocyclylalkyl optionally are substituted with one or two substituents independently selected from the group consisting of alkyl, carboxy, hydroxy, alkyloxy, halo, nitro, cyano, oxo, and amino, and (2) the amino portion of the aminocarbonylalkyl optionally is substituted with one or two substituents independently selected from the group consisting of alkyl, alkenyl, and alkynyl, (b) the alkyl, alkenyl, and alkynyl portion of such substituents optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, halo, oxo, amino, alkyloxycarbonyl, alkylcarbonyloxy, hydroxy, alkyloxy, carbocyclyl, heterocyclyl, and cyano, wherein: the amino optionally is substituted with one or two substituents independently selected from the group consisting of alkyl and alkyloxy, wherein: the alkyl optionally is substituted with one or more hydroxy; and each RK is independently selected from the group consisting of aminosulfonyl and alkylsulfonyl, wherein: (a) the alkylsulfonyl optionally is substituted with one or two substituents independently selected from the group consisting of carboxy, hydroxy, halo, amino, nitro, oxo, aminosulfonyl, alkyloxycarbonyl, alkylcarbonyloxy, alkyloxy, carbocyclyl, heterocyclyl, cyano, and aminocarbonyl; and (b) the aminosulfonyl optionally is substituted with one or two substituents independently selected alkyl. 3. The compound or salt of any one of claims 1 and 2, wherein R6 is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent is substituted with one, two, or three substituents independently selected from the group consisting of RE, RF, R1, RJ, and RK. 4. The compound or salt of any one of claims 1-3, wherein: R1 is hydrogen; R2 is selected from the group consisting of hydrogen and halo; R3 is hydrogen; R4 is tert-butyl; and R is selected from the group consisting of hydroxy and methoxy. 5. The compound or salt of any one of claims 1-4, wherein R6 is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent is substituted with one, two, or three substituents independently selected from the group consisting of RE, RF, and RJ 6. The compound or salt of any one of claims 1-5, wherein: R is selected from the group consisting of fused 2-ring carbocyclyl and fused 2-ring heterocyclyl, wherein each such substituent is substituted with a substituent selected from the group consisting of RF and RJ; RF is alkylsulfonylaminoalkyl; and RJ is alkylsulfonylamino. 7. The compound or salt of any one of claims 1-6, wherein the substituted fused 2-ring carbocyclyl is selected from the group consisting of naphthalenyl, dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl, decahydronaphthalenyl, indenyl, dihydroindenyl, hexahydroindenyl, and octahydroindenyl. 8. The compound or salt of any one of claims 1-6, wherein the substituted fused 2-ring heterocyclyl is selected from the group consisting of (Formula Removed) X5, X6, and X7 are independently selected from the group consisting of N and C(H); X8 is selected from the group consisting of N(H), O, and S; one or more of X19 ,X20 , and X21 is N, and the remaining one(s) is/are C(H); one or more of X22, X23, X24, and X25 is N, and the remaining one(s) is/are C(H); X40, X41, and X42 are independently selected from the group consisting of N and C(H); one of X43, X44, and X45 is selected from the group consisting of N(H), O, and S, and the remaining two are C(H)2; X56, X57, and X58 are independently selected from the group consisting of N and C(H); X59 is selected from the group consisting of N(H), O, and S; one or more of X73, X74, X75, and X76 is N, and the remaining one(s) is/are C(H); and one of X77 and X78 is N(H), and the remaining one is C(H)2. 9. The compound or salt of claim 8, wherein: X5, X6, and X7 are C(H); one of X19, X20, and X21 is N; one of X22, X23, X24, and X25 is N; X40, X41, and X42 are C(H); and X56, X57 and X58 are C(H). 10. A compound or salt thereof, wherein the compound is selected from the group of compounds shown in Tables 1-9. 11. N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide crystalline form selected from the group consisting of: crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.3±0.2, 9.7±0.2, 10.6±0.2, 13.6±0.2, 17.2±0.2, 19.2±0.2, 22.7±0.2, 26.9±0.2, and 29.4±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.3±0.2, 9.7±0.2, 10.0±0.2, 10.6±0.2, 13.6±0.2, 17.2±0.2, 17.5±0.2, 19.2±0.2, 19.4±0.2, 22.7±0.2, 26.9±0.2, and 29.4±0.2 degrees 26; crystalline N-(6-{3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern substantially as shown in Figure 1; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesuIfonamide acetonitrile solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.3±0.2, 8.3±0.2, 9.7±0.2, 10.5±0.2, 13.8±0.2, 17.2±0.2, 19.1±0.2, and 19.5±0.2 degrees 26; crystalline N-(6-{3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yI)methanesuIfonamide acetonitrile solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.3±0.2, 8.3±0.2, 9.7±0.2, 10.5±0.2, 13.8±0.2, 17.2±0.2, 17.7±0.2, 19.1±0.2, 19.5±0.2, 22.0±0.2, 22.8±0.2, and 27.2±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide acetonitrile solvate having an X-ray powder diffraction pattern substantially as shown in Figure 3; crystalline N-(6-{3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide ethyl acetate solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 7.9±0.2, 9.3±0.2, 9.7±0.2, 10.6±0.2, 18.7±0.2, 38.5±0.2, and 44.7±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide ethyl acetate solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 7.9±0.2, 9.3±0.2, 9.7±0.2, 10.6±0.2, 13.7±0.2, 17.4±0.2, 18.7±0.2, 21.7±0.2, 22.0±0.2, 28.2±0.2, 38.5±0.2, and 44.7±0.2 degrees 29. crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide ethyl acetate having an X-ray powder diffraction pattern substantially as shown in Figure 4; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2±0.2, 9.3±0.2, 10.1±0.2, 16.3±0.2, 18.1±0.2, 18.6±0.2, 19.4±0.2,21.6±0.2, and 22.5±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2±0.2, 9.3±0.2, 10.1±0.2, 16.3±0.2, 18.1±0.2, 18.6±0.2, 19.4±0.2, 21.6±0.2, 22.5±0.2, 23.8±0.2, 26.0±0.2, and 28.0±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-{2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern substantially as shown in Figure 5; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.4±0.2, 9.7±0.2, 10.1±0.2, 13.8±0.2, 17.4±0.2, 19.3±0.2, and 19.6±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.4±0.2, 9.7±0.2, 10.1±0.2, 13.5±0.2, 13.8±0.2, 17.4±0.2, 19.3±0.2, 19.6±0.2, and 27.1±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern substantially as shown in Figure 6; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2±0.2, 9.3±0.2, 10.1±0.2, 15.7±0.2, 16.2 ±0.2, 18.4±0.2, 19.3±0.2, 21.6±0.2, and 22.8±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2±0.2, 9.3±0.2, 10.1±0.2, 10.5±0.2, 15.7±0.2, 16.2 ±0.2, 18.4±0.2, 18.6±0.2, 19.3±0.2, 21.0±0.2, 21.6±0.2, and 22.8±0.2 degrees 29; crystalline N-(6-(3-tert-butyi-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern substantially as shown in Figure 7. crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.2±0.2, 7.9±0.2, 9.9±0.2, 16.2±0.2, and 18.3±0.2 degrees 29; crystalline solvent free N-(6-(3-tert-butyI-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.2±0.2, 7.9±0.2, 9.9±0.2, 10.1±0.2, 14.9±0.2, 16.2±0.2, 18.3±0.2, 19.8±0.2, and 26.5±0.2 degrees 29; crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern substantially as shown in Figure 8; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4±0.2, 12.9±0.2, 17.9±0.2, and 18.9±0.2 degrees 29; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4±0.2, 12.9±0.2, 17.5±0.2, 17.9±0.2, 18.9±0.2,and 24.4±0.2 degrees 29; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4±0.2, 12.7±0.2, 12.9±0.2, 14.1±0.2, 15.7±0.2, 17.2±0.2, I7.5±0.2, !7.9±0.2, 18.9±0.2, 21.2±0.2, 24.4±0.2, and 25.0±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern substantially as shown in Figure 9; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yI)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6±0.2, 10.4±0.2, 12.0±0.2, 15.6±0.2, 18.6±0.2, 22.8±0.2, and 23.9±0.2 degrees 26; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthaIen-2-yl)methanesulfonamide monosodium sah having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6±0.2, 10.4±0.2, 12.0±0.2, 15.6±0.2, 18.6±0.2, 22.8±0.2, 23.3±0.2, and 23.9±0.2 degrees 29; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yI)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium sah having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6±0.2, 10.4±0.2, 12.0±0.2, 15.6±0.2, 16.0±0.2, 18.6±0.2, 22.8±0.2, 23.3±0.2, 23.9±0.2, and 28.3±0.2 degrees 29; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern substantially as shown in Figure 10; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4±0.2, 10.8±0.2, 14.4±0.2, 16.3±0.2, 17.0±0.2, 21.6±0.2, 22.1 ±0.2, and 23.7±0.2 degrees 29; crystalline pattern B N-(6-(3-tert-butyI-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4±0.2, 10.8±0.2, 14.4±0.2, 16.3±0.2, 17.0±0.2, 18.8±0.2, 19.2±0.2, 19.6±0.2, 2].6±0.2, 22.1±0.2, 23.7±0.2, 28.8±0.2, 29.1±0.2, and 31.8±0.2 degrees 29; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5.4±0.2, 10.8±0.2, 16.3±0.2, 22.1±0.2, and 23.7±0.2 degrees 29; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising peaks at 5.4±0.2, 10.8±0.2, 16.3±0.2, and 22.1±0.2 degrees 28; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0±0.2, 12.0±0.2, 17.5±0.2, 18.8±0.2, and 22.7±0.2 degrees 20; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0±0.2, 12.0±0.2, 17.5±0.2, 17.8±0.2, 18.8±0.2, and 22.7±0.2 degrees 29; crystalline pattern C N-(6-(3-tert-but>'l-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having pattern C monosodium salt has an X-ray powder diffraction pattern substantially as shown in Figure 14; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl)-naphthalen-2-yl)methanesulfonamide disodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.8±0.2, 9.6±0.2, 10.5±0.2, 13.0±0.2, 14.6±0.2, 15.4±0.2, 16.8 ±0.2, and 23.0±0.2 degrees 26; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide disodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.8±0.2, 9.6±0.2, 10.5±0.2, 13.0±0.2, 14.6±0.2, 15.4±0.2, 16.8 ±0.2, 22.7±0.2, 23.0±0.2, and 23.3±0.2 degrees 20; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide disodium salt having disodium salt has an X-ray powder diffraction pattern substantially as shown in Figure 15; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide monopotassium sah having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0±0.2, 9.9±0.2, 11.3±0.2, 13.3±0.2, 16.9±0.2, 18.1±0.2, 19.1±0.2, 20.0±0.2, 21.1±0.2, 23.5±0.2, 24.8±0.2, and 25.7±0.2 degrees 29; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide monopotassium salt having monopotassium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0±0.2, 9.9±0.2, 11.3±0.2, 13.3±0.2, 16.9±0.2, 18.1±0.2, 19.1±0.2, 20.0^0.2,21.1±0.2, 21.5±0.2, 23,5±0.2, 24.8±0.2, and 25.7±0.2 degrees 29; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide monopotassium salt having an X-ray powder diffraction pattern substantially as shown in Figure 17; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10.9±0.2, 12.1 ±0.2, 13.4±0.2, 15.5±0.2, 17.0±0.2, 17.8±0.2, 18.3±0.2, 19.5±0.2, and 21.9±0.2 degrees 20; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10.9±0.2, 12.1±0.2, 13.0±0.2, 13.4±0.2, 13.6±0.2, 15.5i0.2, 17.0±0.2, 17.8±0.2, 18.3±0.2, 19.5±0.2, 19.7±0.2, and 21.9±0.2 degrees 20; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern substantially as shown in Figure 19; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonaniide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.0±0.2, 9.4±0.2, 11.0±0.2, 13.0±0.2, 13.7±0.2, 15.9±0.2, 17.{)±0.2, 18.3±0.2, 18.9±0.2, 19.8±0.2, and 22.1±0.2 degrees 29; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.0±0.2, 9.4±0.2, 11.0±0.2, 13.0±0.2, 13.3±0.2, 13.7±0.2, 15.9±0.2, 17.0±0.2, 17.4±0.2, 18.3±0.2, 18.9±0.2, 19.8±0.2, 21.8±0.2, and 22.1±0.2 degrees 29; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern substantially as shown in Figure 21; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.6±0.2, ll.OiO.2, 12.9±0.2, 17.0±9.2, 17.5±0.2, 18.9±0.2, 19.8±0.2, and 21.9±0.2 degrees 29; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.6±0.2, 11.0±0.2, 12.9±0.2, 17.9±0.2, ]7.5±0.2, 18.9±0.2, 19.8±9.2, 21.9±0.2, and 22.1±0.2 degrees 29; and crystalline N-(6-(3-tert-buty!-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern substantially as shown in Figure 23. 12. A composition comprising (a) one or more compounds and/or salts recited in any one of claims 1-10 or one or more crystalline forms recited in claim 11; (b) one or more excipients; and, optionally, (c) one or more additional therapeutic agents. 13. A method for inhibiting replication of a ribonucleic acid (RNA) virus, wherein the method comprises exposing the virus to one or more compounds and/or salts recited in any one of claims 1-10 or one or more crystalline forms recited in claim 11. 14. A method for treating hepatitis C in a mammal in need of such treatment, wherein the method comprises administering to the mammal one or more compounds and/or salts recited in any one of claims 1-JO or one or more crystalline forms recited in claim 11, and, optionally, one or more additional therapeutic agents. 15. A process for preparing the compound or salt of claim 1, wherein the process comprises reacting a compound of formula III (wherein R1 R2, and R3 are as defined in claim 1) with a compound of formula IV (wherein R4 and R5 are as defined in claim 1; X1 is halo; and X2 is selected from the group consisting of chloro, bromo, and iodo) in the presence of (i) copper (l) salt catalyst and (ii) nitrogenous heteroaryl ligand (Formula Removed) 16. The process of any one of claims 20 and 21, wherein the process is conducted in the presence of abase. 17. The process of claim 16, wherein the base is selected from the group consisting of potassium salt, sodium salt, and cesium salt. 18. The process of any one of claims 15-17, wherein the nitrogenous heteroaryl ligand comprises a picolinamide compound corresponding in structure to formula V: (FORMULA REMOVED) R11, R12, R13 R14, R15, R16 and R17 are independently selected from the group consisting of hydrogen, C1-4-perfluoroalkyl, C1-4-alkyloxy, C1-4-haloalkyl, chloro, and cyano. 19. The process of any one of claims 15-17, wherein the nitrogenous heteroaryl ligand is selected from the group consisting of 8-hydroxyquinoline, 2-(2-pyridyl)-benzimidazole, N-(4-cyano- phenyl)picolinamide, and N-(2-cyanophenyl)picolinamide. 20. The process of any one of claims 15-19, wherein the copper catalyst is selected from the group consisting of Cul, CuBr, CuCl, Cu2O, and CH3CC(O)Cu.