PROTEIN KINASE INHIBITORS
Technical field
The present invention relates to therapeutically active compounds and pharma-
ceutically acceptable salts thereof which are useful e.g. in the treatment of cancer.
Background of the invention
Protein kinases are a class of proteins (enzymes) that regulate a variety of
cellular functions. This is accomplished by phosphorylation of specific amino acids on
protein substrates resulting in conformational alteration of the substrate protein. The
conformational change modulates the activity of the substrate or its ability to interact
with other binding partners. Tyrosine kinases are a subset of protein kinases that
catalyze the transfer of the terminal phosphate of adenosine triphosphate (ATP) to
tyrosine residues on protein substrates. The human genome contains around 90 tyrosine
kinases and 43 tyrosine kinase like genes, the products of which regulate cellular
proliferation, survival, differentiation, function and motility.
Tyrosine kinases are of two varieties, i.e. receptor and non-receptor tyrosine
kinases. Receptor tyrosine kinases (e.g., FGFR) are trans-membrane proteins with a
ligand-binding extracellular domain and a catalytic intracellular kinase domain, while
non-receptor tyrosine kinases (e.g., c-ABL) lack trans-membrane domains and are found
in the cytosol, nucleus and inner surface of cell membrane. Kinase domains of all
tyrosine kinases have bilobar architecture, with an N-terminal lobe that binds ATP and
magnesium, a C-terminal lobe containing an activation loop, and a cleft between the
lobes to which polypeptide substrates bind.
Receptor tyrosine kinases become activated when ligand binds to the
extracellular domain, resulting in receptor oligomerization and autophosphorylation of a
regulatory tyrosine within the activation loop of the kinase domain. These phenomena

reorient important amino acid residues, thereby enhancing catalytic activity of the
enzyme.
Fibroblast growth factor (FGF) has been recognized as an important mediator of
many physiological processes, such as cell migration, proliferation, survival and
differentiation during development and angiogenesis. There are currently over 25 known
members of the FGF family. The fibroblast growth factor receptor (FGFR) family-
consists of four members with each composed of an extra cellular ligand binding
domain, a single trans-membrane domain and an intracellular cytoplasmic protein
tyrosine kinase domain. Upon stimulation with FGF, FGFRs undergo dimerisation and
transphosphorylation. Upon dimerization, FGFRs activate range of downstream
signaling pathways, such as MAPK and PKB/Akt pathways (Zhou, W. et. al. Chemistry
& Biology, 2010, 17, 285). Abnormal FGFR signaling has been reported in many tumor
types including multiple myeloma, gastric, endometrial, prostate and breast (Squires M.
et. al. Mol. Cancer Ther., September 2011, 10:1542-1552). FGFsalso have role in
tumor angiogenesis and mediate resistance to vascular endothelial growth factor
receptor 2 (VEGFR2) inhibitors (Casanovas, O. et. al., Cancer Cell, 2005, 8, 299).
Consequently, FGF and FGFRs have the potential to initiate and/or promote
tumorigenesis. Due to this, the FGF signaling system happens to be an attractive
therapeutic target, mainly because therapies targeting FGFRs and/or FGF signaling may
affect both the tumor cells and also tumor angiogenesis (Foote, K. M. et. al., WO
2009/019518 Al). Consequently, FGF and FGFRs have the potential to initiate and/or
promote tumorigenesis.
Summary of the invention
It has been found that compounds of formula (I) inhibit or modulate the activity
of certain protein kinases, more specifically protein tyrosine kinases. In particular, it has
been found that the compounds of formula (I) are potent and selective inhibitors of
FGFR kinases. The compounds of the invention have antiproliferative activity and are
particularly useful in the treatment of cancer.

The compounds of the present invention have a structure represented by
formula (I)

wherein
Z is CH or N;
A is a 5 -12 membered heterocyclic ring;
B is a 5 -12 membered carbocyclic or heterocyclic ring;
R1 is H, C1-7 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-7 alkyl, C1-7 alkoxy, amino,
hydroxy C1-7 alkyl, C1-7 alkylamino C1-7 alkyl, -R12-C(O)-R13, -SO2-R14 or -E-R6;
R2 is H, halogen or C1-7 alkyl;
R3 is H, halogen, C1-7 alkyl, C1-7 alkoxy;
R4 is H, halogen C1-7 alkyl or oxo;
R5 is -C(O)R7, -SO2R8 or -C(O)-D-R9;
R6 is an optionally substituted 5-6 membered heterocyclic ring;
R7 is C1-7 alkyl, C3-7 cycloalkyl, C1-7 alkylamino C1-7 alkyl, -NH-R10 or -NH-X-
R11;
R8 is C1-7 alkyl, C3-7 cycloalkyl, phenyl or an optionally substituted 5-6
membered heterocyclic ring;
R9 is phenyl or an optionally substituted 5-6 membered heterocyclic ring;
Rio is C1-7 alkyl or C3-7 cycloalkyl;
Rn is phenyl or an optionally substituted 5-6 membered heterocyclic ring;
R12 is C1-7 alkyl;
R13 is C1-7 alkoxy or amino;
R14 is C1-7 alkyl or C3-7 cycloalkyl;
E is a bond or a C1-7 alkyl;

B is a ring of formula (1"), (2"), (3") or (4");
R1 is H, C1-7 alkyl, C1-7 alkoxy, hydroxy C1-7 alkyl, C1-7 alkylamino C1-7 alkyl or -
E-R6;
R2 is H;
E is a bond or C1-7 alkyl;
R6 is any of the following groups

R3 is H, halogen, C1-7 alkyl, C1-7 alkoxy;
R4 is H or halogen;
R5 is -C(O)R7, -SO2R8 or -C(O)-D-R9;
R7 is C1-7 alkyl, -NH-R10 or -NH-X-R11 ;
R8 is C1-7 alkyl, C3-7 cycloalkyl, phenyl or a group

X is a bond or C1-7 alkyl, and
D is a bond or C1-7 alkyl.
In one subclass of the above preferred classes are compounds of formula (I),
wherein wherein Z is CH. In still another subclass of above preferred classes are
compounds of formula (I), wherein wherein Z is N.

The present invention also provides a pharmaceutical composition comprising a
compound of formula (I) together with a pharmaceutically acceptable carrier.
The present invention provides further a method for the treatment of a condition,
where FGFR kinase inhibition is desired comprising administering to a subject in need
thereof a therapeutically effective amount of a compound of formula (I).
The present invention provides a compound of formula (I) for use in the
treatment of a condition, where FGFR kinase inhibition is desired.
The present invention provides further a method for the treatment of cancer
comprising administering to a subject in need thereof a therapeutically effective amount
of a compound of formula (I).
The present invention provides a compound of formula (I) for use in the
treatment of cancer.
Detailed description of the invention
The compounds of the invention can be prepared by a variety of synthetic routes
analogously to the methods known in the literature using suitable starting materials. The
compounds according to formula (I) can be prepared e.g. analogously or according to
the following reaction Schemes. Some compounds included in the formula (I) can be
obtained by converting the functional groups of the other compounds of formula (I)
obtained in accordance with the following Schemes, by well known reaction steps such
as oxidation, reduction, hydrolysis, acylation, alkylation, amidation, animation,
sulfonation and others. It should be noted that any appropriate leaving groups, e.g. N-
protecting groups, such as a t-butoxycarbonyl (t-BOC) group or a phenylsulfonyl group,
can be used in well known manner during the syntheses in order to improve the
selectivity of the reaction steps

Compounds of formula (I), wherein R5 is -C(O)CH3 can be prepared, for
example, according to Scheme 1, wherein R1, R2, R3, R4, ring A, ring B and Z are as
defined above, and R is hydrogen or alkyl. In the method of Scheme 1, the iV-(3-bromo-
5-nitrophenyl)acetamide [1] is coupled in a suitable solvent such as 1,2-dimethoxy-
ethane with a boronic acid derivative [2] or a suitable ester thereof in the presence of
Pd(dppf)Cl2 and aqueous sodium carbonate at elevated temperature. The nitro group of
the obtained compound [3] is reduced, e.g. with hydrogen and Pd/C catalyst, iron
powder and aqueous calcium chloride or zinc and aqueous ammonium chloride, and the
resulting amine [4] is reacted with compound [5] in a suitable solvent such as DMF in
the presence of potassium fluoride at elevated temperature to obtain compound [6]. In
case Z is CH in the compound [5], X" is suitably fluoro, and when Z is N, X" is
suitably chloro. The nitro group in compound [6] is reduced, e.g. by using zinc and
aqueous ammonium chloride or iron powder and aqueous calcium chloride, and the
resulting amine [7] is heated with formic acid to produce compound [8] in a ring closure
reaction. Finally, compound [10] is obtained by the Suzuki coupling between compound
[8] and a boronic acid derivative [9] or a suitable ester thereof in a suitable solvent such
as 1,2-dimethoxyethane in the presence of Pd(dppf)Cl2 and aqueous sodium carbonate at
elevated temperature.

In case where ring A in the compound [10] is an oxazol-5-yl ring, the compound
[10] can be also prepared according to Scheme 5, wherein ring B, R3, R4 are as defined
above. In this method the compound [4] is treated with 4-fluoro-3-nitrobenzaldehyde
and the resulting compound [20] is thereafter reacted with toluenesulfonylmethyl
isocyanide to produce the oxazol-5-yl compound [21] in a ring closure reaction. The
nitro group of compound [21] can be further reduced, e.g. by hydrogenation, to produce
the corresponding amine, which can be then treated with formic acid according to
Scheme 1 to afford the end product in the ring closure reaction.

In case where ring A in the compound [10] is a heterocycle linked to the carbon
atom of the bicyclic ring via a nitrogen heteroatom, the compound [10] can be also

prepared using Buchwald coupling according to Scheme 6, wherein X', ring B, R|, R2,
R3, R4 are as defined above.

In case where ring A in the compound [10] is an lH-l,2,3-triazol-4-yl ring and
R2 is hydrogen, the compound [10] can be also prepared according to Scheme 7,
wherein X', Z, R1, R3, R4 and ring B, are as defined above. The starting compound [8] is
silylated by reacting with ethynyltrimethylsilane in the presence of tetrakis(triphenyl-
phosphine)palladium(O) (Pd(PPh3)4) and Cu(I)iodide to produce compound [32].
Treatment with TBAF affords the ethynyl compound [33] which can be reacted with
azido compound R1-N3 in a suitable solvent, such as DMSO:THF:water (1:1:1) or
DMSO:DCM:water (1:1:1) to afford compound [34].


In case where ring A in the compound [10] is a 1-methyl-lH-pyrazol-3-yl ring,
the compound [10] can be also prepared according to Scheme 8, wherein R3, R4 and ring
B, are as defined above. In this method the compound [4] is treated with l-(4-fluoro-3-
nitrophenyl)ethanone and the resulting compound [36] is thereafter reacted with DMF
dimethylacetal to produce the oxazol-5-yl compound [37]. Subsequent treatment with
methyl hydrazine produces compound [38] in a ring closure reaction. The nitro group of
compound [38] can be further reduced, e.g. by aqueous ammonium and zinc, to produce
the corresponding amine, which can be then treated with formic acid according to
Scheme 1 to afford the end product in the ring closure reaction.

Various compounds of formula (1), wherein R5 is other than -C(O)CH3, can be
prepared, for example, according to Scheme 10, wherein R1, R2, R3, R4, R7, R8, R9, Z, D,
ring A and ring B are as defined above. The acetamide compound [10] can be converted
to its corresponding amine [24], for example, by heating in ethanol in the presence of a
base, such as aqueous sodium hydroxide or potassium hydroxide, or an acid such as
aqueous HC1. The obtained amine [24] can be used as a starting material for subsequent
reaction steps. The compounds of formula (I), wherein R5 is -SO2R8 can be prepared, for
example, by treating the amine [24] with Cl-SO2R8 in suitable solvent such as DCM in
the presence of pyridine. Compounds of formula (I), wherein Rs is -C(O)R7 and R7 is C1.
7alkyl or C1-7 alkylamino C1-7 alkyl, can be prepared, for example, by reacting the amine
[24] with HOOC-R7 in suitable solvent such as DMF in the presence of 2-(lH-7-
azabenzotriazol-1 -yl)-1,1,3,3 -tetramethyl uronium hexafluorophosphate
methanaminium (HATU) and DIPEA. Compounds of formula (I), wherein R5 is -C(O)-
D-R9 can be prepared, for example, by reacting the amine [24] with HOOC-D-R9 in
suitable solvent such as DMF in the presence of EDC, HOBt and DIPEA. Compounds
of formula (I), wherein R5 is -C(O)-D-R9, D is a bond and R9 is a heterocyclic ring
linked to the carbonyl carbon atom via nitrogen heteroatom, can be prepared by reacting
the amine [24] with phosgene and then with compound [29] as shown in Scheme 10.

presence of suitable base such as triethylamine (TEA). Alternatively, compounds
wherein R5 is -NH-X-Rn can be prepared by treating amine [24] in suitable solvent such
as DCM with phosgene and then with H2N-X-Rn, see Scheme 11.

Pharmaceutically acceptable salts, e.g. acid addition salts with both organic and
inorganic acids are well known in the field of pharmaceuticals. Non-limiting examples
of these salts include chlorides, bromides, sulfates, nitrates, phosphates, sulfonates,
formates, tartrates, maleates, citrates, benzoates, salicylates and ascorbates.
Pharmaceutically acceptable esters, when applicable, may be prepared by known
methods using pharmaceutically acceptable acids that are conventional in the field of
pharmaceuticals and that retain the pharmacological properties of the free form. Non-
limiting examples of these esters include esters of aliphatic or aromatic alcohols, e.g.
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl esters. Phosphate
esters and carbonate esters, are also within the scope of the invention.

The terms employed herein have the following meanings:
The term "halo" or "halogen", as employed herein as such or as part of another
group, refers to chlorine, bromine, fluorine or iodine.
The term "C1-7 alkyl", as employed herein as such or as part of another group,
refers to a straight or branched chain saturated hydrocarbon group having 1, 2, 3, 4, 5, 6
or 7 carbon atom(s). Representative examples of C1-7 alkyl include, but are not limited
to, methyl, ethyl, n-propyl, iso-propyl, «-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,
iso-pentyl, n-hexyl, and the like. The term "C1-3 alkyl" means an embodiment of "C1-7
alkyl" having 1, 2 or 3 carbon atoms.
The term "C3-7 cycloalkyl", as employed herein as such or as part of another
group, refers to a saturated cyclic hydrocarbon group containing 3, 4, 5, 6 or 7 carbon
atoms. Representative examples of cycloalkyl include, but are not limited to, cyclo-
propyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
The term "C3-7 cycloalkyl C1-7 alkyl", as employed herein refers to a C3-7 cyclo-
alkyl group, as defined herein, appended to the parent molecular moiety through a C1-7
alkyl group, as defined herein.
The term "C2-7 alkenyl", as employed herein as such or as part of another group,
refers to an aliphatic hydrocarbon group having 2 to 7 carbon atoms and containing one
or several double bonds. Representative examples include, but are not limited to,
ethenyl, propenyl and cyclohexenyl and the like.
The term "hydroxy", as employed herein as such or as part of another group,
refers to an -OH group.The term "cyano", as employed herein as such or as part of
another group, refers to a -CN group. The term "amino", as employed herein as such or
as part of another group, refers to a -NH2 group. The term "carboxy", as employed
herein as such or as part of another group, refers to -COOH group. The term "carbonyl",

as employed herein as such or as part of another group, refers to a carbon atom double-
bonded to an oxygen atom (C=0).
The term "C1-7 alkoxy", as employed herein as such or as part of another group,
refers to C1-7 alkyl, as defined herein, appended to the parent molecular moiety through
an oxygen atom. Representative examples of C1-7 alkoxy include, but are not limited to
methoxy, ethoxy, propoxy, butoxy, isobutoxy, sec-hvAoxy, tert-butoxy, and the like.
The term "hydroxyl C1-7 alkyl", as employed herein, refers to at least one
hydroxy group, as defined herein, appended to the parent molecular moiety through a
C1-7 alkyl group, as defined herein. Representative examples of hydroxyl C1-7 alkyl
include, but are not limited to, hydroxymethyl, 2,2-dihydroxyethyl, 1-hydroxyethyl, 3-
hydroxypropyl, 1-hydroxypropyl, 1-methyl-1-hydroxyethyl, 1-methyl-1-hydroxypropyl,
and the like.
The term "halo C1-7 alkyl", as employed herein, refers to at least one halogen, as
defined herein, appended to the parent molecular moiety through a C1-7 alkyl group, as
defined herein. Representative examples of halo C1-7 alkyl include, but are not limited
to, fluoromethyl, difluoromethyl, trifluoromethyl, 2-chloroethyl, 3-bromopropyl, and the
like.
The term "cyano C1-7 alkyl", as employed herein, refers to a cyano group, as
defined herein, appended to the parent molecular moiety through a C1-7 alkyl group, as
defined herein. Representative examples of cyano C1-7 alkyl include, but are not limited
to, cyanomethyl, 1-cyanoethyl, 1-cyanopropyl, 2-cyanopropyl, and the like.
The term "carboxy C1-7 alkyl", as employed herein as such or as part of another
group, refers to a carboxy group, as defined herein, appended to the parent molecular
moiety through a C1-7 alkyl group, as defined herein.

The term uhalogen C1-7 alkoxy", as employed herein, refers to at least one
halogen, as defined herein, appended to the parent molecular moiety through a C1-7
alkoxy group, as defined herein.
The term "C1-7 alkoxycarbonyl", as employed herein as such or as part of another
group, refers to a C1-7 alkoxy group, as defined herein, appended to the parent molecular
moiety through a carbonyl group, as defined herein.
The term "aminocarbonyl", as employed herein as such or as part of another
group, refers to an amino group, as defined herein, appended to the parent molecular
moiety through a carbonyl group, as defined herein.
The term "amino C1-7 alkyl", as employed herein, refers to at least one amino
group, as defined herein, appended to the parent molecular moiety through a C1-7 alkyl
group, as defined herein. Representative examples of amino C1-7 alkyl include, but are
not limited to, aminomethyl, 2-aminoethyl, 1 -aminoethyl, 2,2-diaminoethyl, 3-
aminopropyl, 2-aminopropyl, 4-aminobutyl, 1-methyl-1-aminoethyl, and the like.
The term "C4-7 alkylamino", as employed herein as such or as part of another
group, refers to at least one C1-7 alkyl group, as defined herein, appended to the parent
molecular moiety through an amino group, as defined herein. Representative examples
of C1-7 alkylamino include, but are not limited to methylamino, ethylamino,
propylamino, butylamino, dimethylamino, diethylamino, N-ethyl-N-methylamino, and
the like.
The term "carboxy C1-7 alkylamino", as employed herein as such or as part of
another group, refers to at least one carboxy group, as defined herein, appended to the
parent molecular moiety through an C1-7 alkylamino group, as defined herein
The term "C1-7 alkoxy C1-7 alkyl", as employed herein, refers to at least one C1-7
alkoxy group, as defined herein, appended to the parent molecular moiety through an
C1-7 alkyl group, as defined herein.

The term "C1-7 alkoxycarbonyl C1-7 alkyl", as employed herein, refers to at least
one C1-7 alkoxycarbonyl group, as defined herein, appended to the parent molecular
moiety through an C1-7 alkyl group, as defined herein.
The term "substituted" as used herein in connection with various residues refers
to halogen substituents, such as fluorine, chlorine, bromine, iodine, or C1-7 alkyl, C3-7
cycloalkyl, halo C1-7 alkyl, hydroxy, amino, C1-7 alkoxy, C1-7 acyl CM alkylamino, amino
CM alkyl, nitro, cyano, thiol or methylsulfonyl substituents. Preferred are halogen, CM
alkyl, halo CM alkyl, hydroxy, amino, CM alkoxy and methylsulfonyl substituents.
The "substituted" groups may contain 1 to 3, preferably 1 or 2, most preferably 1
of the above mentioned substituents.
The definition of formula (I) above is inclusive of all the possible stereoisomers
of the compounds, including geometric isomers, e.g. Z and E isomers (cis and trans
isomers), and optical isomers, e.g. diastereomers and enantiomers, and all prodrug
esters, e.g. phosphate esters and carbonate esters, and isotopes. Furthermore, the
invention includes in its scope both the individual isomers and any mixtures thereof, e.g.
racemic mixtures. The individual isomers may be obtained using the corresponding
isomeric forms of the starting material or they may be separated after the preparation of
the end compound according to conventional separation methods. For the separation of
optical isomers, e.g. enantiomers, from the mixture thereof the conventional resolution
methods, e.g. fractional crystallisation, may be used.
Compounds of the invention may be administered to a patient in therapeutically
effective amounts which range usually from about 0.1 to about 1000 mg per day
depending on the age, weight, ethnic group, condition of the patient, condition to be
treated, administration route and the protease inhibitor used. The compounds of the
invention can be formulated into dosage forms using the principles known in the art.
The compound can be given to a patient as such or in combination with suitable
pharmaceutical excipients in the form of tablets, granules, capsules, suppositories,

emulsions, suspensions or solutions. Choosing suitable ingredients for the composition
is a routine for those of ordinary skill in the art. Suitable carriers, solvents, gel forming
ingredients, dispersion forming ingredients, antioxidants, colours, sweeteners, wetting
compounds and other ingredients normally used in this field of technology may be also
used. The compositions containing the active compound can be given enterally or
parenterally, the oral route being the preferred way. The contents of the active
compound in the composition is from about 0.5 to 100 %, preferably from about 0.5 to
about 20 %, per weight of the total composition.
The compounds of the invention can be given to the subject as the sole active
ingredient or in combination with one of more other active ingredients for treatment of a
particular disease, for example cancer.
The present invention will be explained in more detail by the following
experiments and examples. The experiments and examples are meant only for
illustrating purposes and do not limit the scope of the invention defined in claims.
EXPERIMENTS
1. Inhibition of FGFR1 and other kinases
Methods
FGFR1 assay
Compounds were screened in the TR-FRET assay with FGFR1 kinase. 5 ng of
FGFR1 [Upstate, USA] kinase was used for assay. The compound was incubated with
the kinase for 30 minutes at room temperature. After the incubation, substrate mix [40
nM Ultra light poly GT (Perkin Elmer, USA) and 13 uM ATP (Sigma)] was added. The
above reaction was stopped by the addition of 40mM EDTA after the 30 min kinase
reaction. The Eu-labelled antiphospho-tyrosine antibody [Perkin Elmer, USA] was

added at 0.5 nM and the fluorescence emission at 615 nm/665 nm [excitation at 340 nm]
was measured. The compounds were initially screened at 100 nM and 1 uM
concentrations. The compounds with >50 % inhibition at 100 nM of FGFR1 were taken
for the full dose response studies. The final DMSO concentration in the assay was 1 %.
For IC50 determination, l/3rd serial dilution was made from the 20 mM DMSO stock
solution. 2 ul of these were transferred to the test wells containing 20 J_L1 of the reaction
mixture [total reaction volume 20 ul]. The fluorescence was measured in Perkin Elmer
Wallac 1420 Multilabel Counter Victor 3. The IC50 was determined by fitting the dose
response data to sigmoidal curve fitting equation using GraphPad Prism software V5.
c-Met assay
Compounds were screened in the TR-FRET assay with c-Met kinase. 0.1 ng of c-
Met [expressed in-house] kinase was used for assay. The compound was incubated with
the kinase for 60 min at room temperature. After the incubation, substrate mix [40 nM
Ultra light poly GT (Perkin Elmer, USA) and 10 uM ATP (Sigma)] was added. The
above reaction was stopped by the addition of 40 mM EDTA after the 30 min kinase
reaction. The Eu-labelled antiphospho-tyrosine antibody [Perkin Elmer, USA] was
added at 0.5 nM and the fluorescence emission at 615 nm/665 nm [excitation at 340 nm]
was measured. The compounds were initially screened at 1 OOnM and 1 uM
concentrations. The compounds with >50 % inhibition at 100 nM of c-Met were taken
for the full dose response studies. The final DMSO concentration in the assay was 1 %.
For IC50 determination, 1/3rd serial dilution was made from the 20 mM DMSO stock
solution. 2 ul of these were transferred to the test wells containing 20 ul reaction
mixture [total reaction volume 20 ul]. The fluorescence was measured in Perkin Elmer
Wallac 1420 Multilabel Counter Victor 3. The IC50 was determined by fitting the dose
response data to sigmoidal curve fitting equation using GraphPad Prism software V5.
Results

Enzymatic activity and selectivity of selected compounds of the invention on
different kinases is presented in Table 1. The compounds of the invention were found to
be potent and selective FGFR kinase inhibitors.


The preparation of the compounds of the invention is illustrated by the following
Examples.
EXAMPLES.
LCMS data has been recorded in +ve mode unless otherwise mentioned.
Intermediate Example 1.
A^-dimethyl-2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-
yl)ethanamine
a) 2-(4-bromo-1 H-pyrazol-1 -y\)-N, N-dimethylethanamine
To a solution of 4-bromo-lH-pyrazole (5 g, 34 mmol) in DMF were added
potassium carbonate (11.75 g, 85.03 mmol, 2.5 eq.) and 2-chloro-A/',N-dimethylethan-
amine hydrochloride (7.35 g, 51 mmol, 1.5 eq.) and the mixture was stirred at room
temperature for 12 h. The reaction mixture was quenched with water and extracted with
DCM (3 x 150 ml). The combined organic layer was washed with water, brine and dried
over sodium sulphate. The solvent was distilled off under reduced pressure to afford the
crude residue which was purified by column chromatography (60-120 silica gel, 1 %
methanol in DCM) to give the title product in 86 % yield (6.4 g). 1H NMR (300 MHz,
DMSO-4): δ 7.95 (s, 1H), 7.25 (s, 1H), 4.18 (t, 2H), 2.61 (t, 2H), 2.15 (s, 6H); LC-MS
(ESI): Calculated mass: 218.09; Observed mass: 219.8[M+H]+ (RT: 0.439 mm).
b)jyA-dimethyl-2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-
l-yl)ethanamine
To a degassed (N2 bubbling) solution of 2-(4-bromo-l H-pyrazol- l-yl)-N,N-
dimethylethanamine (10 g, 45.85 mmol) in 1,4-dioxane (50 ml) were added
4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (17.47 g, 68.78 mmol, 1.5 eq.),
Pd(dppf)Cl2 (1.87 g, 2.29 mmol, 0.05 eq.) and potassium acetate (11.23 g, 114.6 mmol,
2.5 eq.) and the mixture was heated at 100 CC in a sealed tube for 12 h. The mixture was
diluted with ethyl acetate and filtered over a pad of celite. The solvent was distilled off

under reduced pressure to afford the title product (7.0 g). LC-MS (ESI): Calculated
mass: 265.16; Observed mass: 266.2 [M+H]+ (RT: 0.09 min).
Intermediate Example 2.
4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H-pyrazol-1-yl)ethyl)-
morpholine
The title compound was synthesized using the procedure described in Example 1.
LC-MS (ESI): Calculated mass: 307.2; Observed mass: 308.1 [M+H]+ (RT: 0.11 min).
Intermediate Example 3.
1 -fluoro-4-iodo-2-nitrobenzene
To a solution of 1-fluoro-2-nitrobenzene (5 g, 35.43 rnmol) in triflic acid (15.6
ml, 177.15 rnmol, 5 eq.) at 0 °C was added N-iodosuccinimide (9.57 g, 42.5 mmol, 1.2
eq.) portion wise and the mixture was stirred at room temperature for 1 h. The mixture
was quenched by the addition of water and extracted with diethylether (3 x 150 ml). The
combined organic layer was washed with water, aqueous sodium thiosulfate, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure and the
crude residue was purified by column chromatography (60-120 silica gel, 5 % ethyl
acetate in hexane) to afford the title compound in 66 % yield (6.2 g). 1H NMR (300
MHz, DMSO-d6): δ 8.42 (dd, 1H), 8.18-8.13 (m, 1H), 7.46-7.39 (m, 1H).
Intermediate Example 4.
4-fluoro-3-nitrobenzaldehyde
Nitration mixture (sulfuric acid 40 ml + nitric acid 5.5 ml) was added dropwise
to 4-fluorobenzaldehyde (10 g, 80.57 mmol) at 0 °C and the mixture was stirred at 5 °C
for 20 min and room temperature for 1 h. The reaction mixture was quenched by the
addition of crushed ice. The precipitate formed was filtered and was washed repeatedly
with water to obtain white solid. The solid was dried under high vacuum to give the

product in 77 % yield (10.5 g). lH NMR (300 MHz, CDC13): δ 10.04 (s, 1H), 8.58 (dd,
1H), 8.22-8.18 (m, 1H), 7.5 (t, 1H).
Intermediate Example 5.
tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-lH-pyrazol-1 -yl)-
piperidine-1 -carboxylate
a) tert-butyl 4-hydroxypiperidine-l-carboxylate
To a solution of piperidin-4-ol (3.5 g, 34.6 mmol) in CH2C12 (50 ml) at 0 °C
were added Boc20 (11.3 g, 51.9 mmol, 1.5 eq.) and Et3N (7.2 ml, 51.9 mmol, 1.5 eq.)
and the mixture was stirred at room temperature for 1 h. The reaction mixture was then
quenched with water and extracted with DCM (3 x 100 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure to afford the crude product (7.0 g).
b) tert-butyl 4-(methylsulfonyloxy)piperidine-l-carboxylate
tert-Butyl 4-hydroxypiperidine-l-carboxylate (7 g, 34.7 mmol) was dissolved in
CH2C12 (70 ml) at 0 °C followed by the addition of Et3N (10 ml, 69.4 mmol, 2 eq.) and
methanesulfonyl chloride (2.7 ml, 34.7 mmol, 1 eq.) and the mixture was stirred at room
temperature for 3 h at which time it was quenched by the addition of water and extracted
with DCM (3 x 100 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the crude product (6.7 g).
c) tert-butyl 4-(4-bromo-lH-pyrazol-l-yl)piperidine-l-carboxylate
To a cooled solution of tert-butyl 4-(methylsulfonyloxy)piperidine-1 -carboxylate
(6.7 g, 23.9 mmol) in DMF (50 ml) was added NaH (2.8 g, 119 mmol, 5 eq.) and 4-
bromo-lH-pyrazole (2.8 g, 19.1 mmol, 0.8 eq.) and stirred at 80 °C for 12 h. The
reaction mixture was then quenched with water and extracted with ethyl acetate (3 x 100

ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure to afford the crude
product (8.0 g).
d)/ert-butyl4-(4-(4,4,5,5-tetramethyl-L3,2-dioxaborolan-2-yl)-lH-p>Tazol-l-
yl)piperidine-1 -carboxylate
To a degassed (N2 bubbling) solution of terf-butyl 4-(4-bromo-lH-pyrazol-l-yl)-
piperidine-1-carboxylate (8 g, 24.2 mmol) in 1,4-dioxane (100 ml) were added 4,4,4',4',-
5,5,5',5'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (7.36 g, 29 mmol, 1.2 eq.), Pd(dppf)Cl2
(2 g, 2.42 mmol, 0.1 eq.) and potassium acetate (8 g, 82.4 mmol, 3.4 eq.) and the
mixture was heated at 110 °C in a sealed tube for 12 h. The mixture was diluted with
ethyl acetate and filtered over a pad of celite. The solvent was distilled off under
reduced pressure and the residue was purified by column chromatography (60-120 silica
gel, 10 % ethyl acetate in hexane) to give the title product in 59 % yield (5.4 g). LC-MS
(ESI): Calculated mass: 377.29; Observed mass: 378.3 [(M+H]+ (RT: 1.83 min).
Intermediate Example 6.
4-azido-2-methylbutan-2-ol
a) 4-bromo-2-methylbutan-2-ol
To a cooled solution of ethyl 3-bromopropanoate (0.5 g, 2.8 mmol) in diethyl
ether (50 ml) at 0 °C was added methyl magnesium bromide (0.98 g, 8.3 mmol, 3 eq.)
dropwise over a period of 5 min and the mixture was allowed to stir until TLC showed
complete absence of the starting material. The reaction mixture was quenched with
water and extracted with ethyl acetate (3*50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure to afford the crude product (0.4 g).
b) 4-azido-2-methylbutan-2-ol

To a mixture of 4-bromo-2-methylbutan-2-ol (0.4 g, 2.4 mmol) and triethylamine
(1 ml, 7 mmol, 3 eq.) in CH2CI2 (15 ml) was added sodium azide (0.47 g, 7 mmol, 3 eq.)
in H20 (5 ml) and the mixture was allowed to stir overnight. The mixture was quenched
with water and extracted with CH2C12 (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure to afford the product in 65 % yield (0.2 g). 1H NMR (300 MHz,
DMSO-d6): δ 4.39 (br s, 1H), 3.40-3.32 (m, 2H), 1.15 (t, 2H), 1.23-1.04 (m, 6H).
Intermediate Example 7.
Azidocyclopentane
To a solution of iodocyclopentane (0.5 g, 2.55 mmol) in DMF (2 ml) was added
aqueous sodium azide (0.33 g, 5.1 mmol) and stirred at room temperature for 10 min,
followed by stirring at 80 °C overnight. The mixture was extracted with diethyl ether (3
x 50 ml) and the combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the
product in 64 % yield (0.18 g) which was directly used for the next step. FTIR (neat): v
3448, 2471,2100, 1671, 1498, 1438, 1383, 1256, 1094, 865 cm"1.
Intermediate Example 8.
(Azidomethyl)cyclobutane
To a solution of (bromomethyl)cyclobutane (0.5 g, 3.35 mmol) in DMF (2 ml)
was added aqueous sodium azide (0.43 g, 6.7 mmol). The mixture was stirred at room
temperature for 10 min, followed by stirring at 80 °C overnight. The mixture was
extracted with diethyl ether (3x50 ml) and the combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure to give the product in 54 % yield (0.2 g). 1H NMR (300 MHz, DMSO-
d6): δ 3.66-3.53 (m, 2H), 2.66-2.21 (m, 1H), 2.06-2.00 (m, 2H), 1.84-1.66 (m, 4H).
Intermediate Example 9.

1 -(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3.2-dioxaborolan-2-yl)-lH-
pyrazole
a) 4-bromo-1 -(cyclopropylmethyl)-1 H-pyrazole
To a solution of 4-bromo-1 H-pyrazole (0.1 g, 0.68 mmol) in DMF (20 ml) were
added K2CO3 (0.19 g, 1.36 mmol, 2 eq.) and (bromomethyl)cyclopropane (92 mg, 0.68
mmol, 1 eq.). The mixture was stirred at room temperature for 4 h. The mixture was
quenched with water and extracted with ethyl acetate (3 * 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the crude product (0.15 g).
b) l-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-
pyrazole
To a degassed (N2 bubbling) solution of 4-bromo-1 -(cyclopropylmethyl)- 1H-
pyrazole (0.15 g, 0.75 mmol) in 1,4-dioxane (10 ml) were added 4,4,4',4',5,S,5',5'-octa-
methyl-2,2'-bi(l,3,2-dioxaborolane) (0.23 g, 0.9 mmol, 1.2 eq.), Pd(dppf)Cl2 (0.12 g,
0.15 mmol, 0.2 eq.) and potassium acetate (0.25 g, 2.55 mmol, 3.4 eq.) and the mixture
was heated at 110 °C in a sealed tube for 12 h. The mixture was diluted with ethyl
acetate and filtered over a pad of celite. The solvent was distilled off under reduced
pressure to afford the crude residue which was purified by column chromatography (60-
120 silica gel, 30 % ethyl acetate in hexane) to give the title product in 81 % yield (0.15
g). LC-MS (ESI): Calculated mass: 248.13; Observed mass: 249.2 [(M+Hf (RT: 1.58
min).
Intermediate Example 10.
2-Morpholinoacetic acid
a) Ethyl 2-morphoIinoacetate
To a solution of ethyl 2-chloroacetate (0.5 g, 5.74 mmol) in DMF (70 ml) at 10
°C were added potassium carbonate (1.98 g, 14.34 mmol, 2.5 eq.) and 1-mcthylpipcra-

zine (1.05 g, 8.6 mmol, 1.5 eq.) and the mixture was stirred at room temperature for 2 h.
The reaction mixture was quenched with water and extracted with ethyl acetate (3*50
ml). The combined organic layer was washed with water and brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the crude
residue was purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in
hexane) to afford the title product in 74 % yield (0.74 g). LC-MS (ESI): Calculated
mass: 173.2, Observed mass: 174.0 [M+H]+ (RT: 0.20 min).
b) 2-morpholinoacetic acid
A solution of ethyl 2-morpholinoacetate (1.8 g, 11.44 mmol) in 8 N HC1 (5 ml)
was heated at 90 °C for 12 h. The mixture was concentrated under reduced pressure to
afford the title product in 64 % yield (0.9 g). LC-MS (ESI): Calculated mass: 145.16;
Observed mass: 146.3 [M+H]+ (RT: 0.21 min).
Intermediate Example 11.
4-Azido-1 -methylpiperidine
a) 1 -Methylpiperidin-4-yl methanesulfonate
l-Methylpiperidin-4-ol (4 g, 34.7 mmol) was dissolved in CH2C12 (70 ml) at 0
°C followed by the addition of Et3N (10 ml, 69.4 mmol, 2 eq.) and methanesulfonyl
chloride (2.7 ml, 34.7 mmol, 1 eq.) and the mixture was stirred at room temperature for
3 h at which time it was quenched by the addition of water and extracted with DCM (3 x
100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the
crude product (6.7 g).
b) 4-azido-l-methylpiperidine
To a solution of 1 -methylpiperidin-4-yl methanesulfonate (2.1 g, 10.9 mmol) in
DMF (30 ml) was added sodium azide (1 g, 16.32 mmol, 1.5 eq.) and the mixture was

stirred at 60 °C for 12 h. The mixture was then quenched with water and extracted with
diethylether (3 * 100 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure to
give the desired product (1.3 g). 1H NMR (300 MHz, CDC13): δ 3.49-3.37 (m, 1H),
2.71-2.67 (m, 2H) 2.24 (s, 3H) 2.18-2.09 (m, 2H) 1.93-1.85 (m, 2H) 1.72-1.60 (m, 2H);
LC-MS (ESI); Calculated mass: 140.1: Observed mass: 141.1 [M+H]+ (RT: 0.13 min).
Intermediate Example 12.
l-Isopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole
a) 4-Bromo-1 -isopropyl-1 H-pyrazole
To a solution of 4-bromo-l H-pyrazole (5 g, 34 mmol) in DMF (70 ml) were
added potassium carbonate (11.83 g, 85.6 mmol, 2.5 eq.) and 2-bromopropane (6.3 g,
51.36 mmol, 1.5 eq.) and the mixture was stirred at room temperature for 12 h. The
reaction mixture was quenched with water and extracted with DCM (3 x 150 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the crude residue was purified
by column chromatography (60-120 silica gel, 20 % ethyl acetate in hexane) to afford
the title product in 89 % yield (5.8 g). lU NMR (300 MHz, DMSO-d6): δ 8.01 (s, 1H),
7.50 (s, 1H), 4.49-4.43 (m, 1H), 1.38 (d, 6H).
b) 1 -Isopropyl-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-l H-pyrazole
To a degassed (N2 bubbling) solution of 4-bromo-l-isopropyl-1 H-pyrazole (1.5
g, 7.9 mmol) in 1,4-dioxane (30 ml) were added 4,4,4',4',5,5,5',5,-octamethyl-2,2,-
bi(l,3,2-dioxaborolane) (3 g, 11.84 mmol, 1.5 eq.), Pd(dppf)Cl2 (0.64 g, 0.79 mmol, 0.1
eq.) and potassium acetate (1.93 g, 19.74 mmol, 2.5 eq.) and the mixture was heated at
100 °C in a sealed tube for 12 h. The mixture was diluted with ethyl acetate and filtered
over a pad of celite. The solvent was distilled off under reduced pressure to afford the
title product in 67 % yield (1.2 g). LC-MS (ESI): Calculated mass: 236.12; Observed
mass: 237.1 [M+H]+(RT: 1.41 min).

Intermediate Example 13.
l-Ethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole
a) 4-Bromo-l-ethyl-lH-pyrazole
To a solution of 4-bromo-lH-pyrazole (5 g, 34 mmol) in DMF were added
potassium carbonate (11.75 g, 85.03 mmol, 2.5 eq.) and iodoethane (8 g, 51 mmol, 1.5
eq.) and the mixture was stirred at room temperature for 12 h. The reaction mixture was
quenched with water and extracted with DCM (3 x 150 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure and the crude residue was purified by column chromato-
graphy (60-120 silica gel, 40 % ethyl acetate in hexane) to yield the title product in 84 %
yield (5 g). 1H NMR (300 MHz, DMSO-d6): δ 8.02 (s, 1H), 7.55 (s, 1H), 4.15 (q, 2H),
1.37 (t, 3H); LC-MS (ESI): Calculated mass: 175.03; Observed mass: 177.0 [M+H]+
(RT: 0.56 min).
b) l-Ethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole
To a degassed (N2 bubbling) solution of 4-bromo-l-ethyl-lH-pyrazole (2 g,
11.42 mmol) in 1,4-dioxane (30 ml) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-
bi(l,3,2-dioxaborolane) (4.35 g, 17.14 mmol, 1.5 eq.), Pd(dppf)Cl2 (0.93 g, 1.14 mmol,
0.1 eq.) and potassium acetate (2.79 g, 28.55 mmol, 2.5 eq.) and the mixture was heated
at 100 °C in a sealed tube for 12 h. The mixture was diluted with ethyl acetate and
filtered over a pad of celite. The solvent was distilled off under reduced pressure to
afford the title product in 88 % yield (2.2 g). LC-MS (ESI): Calculated mass: 222.09;
Observed mass: 223.3 [M+H]+ (RT: 0.83 min).
Intermediate Example 14.
2-chloro-5 -iodo-3 -nitropyridine
a) 5-iodo-3-nitropyridin-2-amine

To a solution of 3-nitropyridin-2-amine (1.2 g, 8.63 mmol) in acetic acid (5 ml),
water (1 ml) and sulfuric acid (0.2 ml) was added periodic acid (0.4 g. 1.72 mmol, 0.2
eq.) and the mixture was stirred at 90 °C for 15 min. Iodine (0.87 g, 3.45 mmol, 0.4 eq.)
was added portionwise and the mixture was heated at 90 °C for 1 h. The reaction
mixture was quenched by the addition of water and extracted with ethylacetate (3 x 150
ml). The combined organic layer was washed with water, aqueous sodium thiosulfate,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 57 % yield (1.3 g). JH NMR (300 MHz, DMSO-
ck): δ 8.58 (d, 1H), 8.54 (d, 1H) 8.04 (br s, 2H); LC-MS (ESI); Calculated mass; 265.01:
Observed mass: 265.9 [M+H]+ (RT: 1.36 min).
b) 2-chloro-5-iodo-3-nitropyridine
To a solution of 5-iodo-3-nitropyridin-2-amine (1.3 g, 4.9 mmol) in concentrated
HC1 at 0 °C was added sodium nitrite (6.73 g, 97.13 mmol, 20 eq.) stepwise followed by
the addition of copper(I) chloride (0.5 g, 4.9 mmol, 1 eq.) and the mixture was stirred at
room temperature for 12 h. The reaction mixture was then poured in to a mixture of
ammonium hydroxide and water (1:1) and extracted with ethylacetate (3 x 150 ml). The
combined organic layer was washed with water, aqueous sodium thiosulfate, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 43 % yield (0.6 g).
Example 1.
N-(2',4,-difluoro-5-(5-( 1-methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1-
yl)biphenyl-3 -yl)acetamide
a) l-bromo-3,5-dinitrobenzene
To a solution of 1,3-dinitrobenzene (25 g, 0.149 mol) in concentrated sulfuric
acid (100 ml) at 0 °C was added l,3-dibromo-5,5-dimethylhydantoin (31.75 g, 0.111
mol, 0.75 eq) portionwise over a period of 30 min. The mixture was stirred for 12 at

room temperature and quenched by the addition of crushed ice. The precipitate formed
was filtered and was washed repeatedly with water to obtain white solid. The solid was
dried under high vacuum to give the product in 87 % yield (32 g).
b) 3-bromo-5-nitroaniline
To a solution of l-bromo-3,5-dinitrobenzene (20 g, 80.97 mmol) in acetic acid
(120 ml) at 90 °C was added iron powder (11.3 g, 202.4 mmol, 2.5 eq) slowly portion-
wise over a period of 30 min (caution: highly exothermic reaction). After completion of
the addition, the reaction mixture was quenched by the addition of crushed ice. The
precipitate formed was filtered and was washed with cold water to obtain orange solid.
The solid was dried under high vacuum to give the title product in 80 % yield (14 g). H
NMR (300 MHz, CDC13): δ 10.55 (br s, 2H), 8.46 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H).
c) N-(3-bromo-5-nitrophenyl)acetamide
Acetic anhydride (14 ml) was added dropwise at 0 °C to 3-bromo-5-nitroaniline
(14 g, 64.5 mmol). The mixture was stirred for 30 min at room temperature and then
quenched by the addition of crushed ice. The precipitate formed was filtered and washed
with cold water to obtain off-white solid. The solid was dried under high vacuum to give
the title product in 78 % yield (13 g). 1H NMR (300 MHz, DMSO-d6): δ 10.54 (br s,
1H), 8.45 (s, 1H), 8.2 (s, 1H), 8.03 (s, 1H), 2.11 (s, 3H).
d) AA-(2',4'-difiuoro-5-nitrobiphenyl-3-yl)acetamide
A solution of A^-(3-bromo-5-nitrophenyl)acetamide (1 g, 3.86 mmol) in 1,2-
dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. 2,4-Difluorophenyl-
boronic acid (0.727 g, 4.63 mmol, 1.2 eq.) was added and the mixture was degassed for
another 5 min. Pd(dppf)Cl2 (0.627g, 0.769 mmol, 0.2 eq.) and aqueous sodium
carbonate (1.22 g, 11.5 mmol, 3.0 eq.) were added sequentially and the mixture was
further degassed for 5 min and then heated at 90 °C for 2 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3><50 ml). The combined organic

layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure and the crude residue was purified by column
chromatography (60-120 silica gel, 30 % ethyl acetate in hexane) to give the title
product in 80 % yield (0.9 g). *H NMR (300 MHz, DMSO-d6): δ 10.63 (s, 1H), 8.7-8.69
(m, 1H), 8.16 (d, 1H), 8.04 (s, 1H), 7.8-7.67 (m, 1H), 7.53 (m, 1H), 7.34 (m, 1H), 2.19
(s, 3H).
e)iV-(5-amino-2',4'-difluorobiphenyl-3-yl)acetamide
To a solution of N-(2,,4'-difluoro-5-nitrobiphenyl-3-yl)acetamide (4 g, 13.7
mmol) in methanol (30 ml) and ethyl acetate (15 ml) was added 10 % Pd/C (400 mg, 0.1
eq.) and the reaction vessel was purged with nitrogen gas for 5 min. The mixture was
then hydrogenated with H2 balloon for 12 h. The mixture was filtered through a pad of
celite and the filtrate was concentrated under reduced pressure to afford the title
compound in 89 % yield (3.2g). 1H NMR (300 MHz, DMSO-d6): δ 9.77 (br s, 1H),
7.46-7.42 (m, 1H), 7.35-7.28 (m, 1H), 7.2-7.15 (m, 1H), 6.99 (br s, 1H), 8.86 (d, 1H),
6.39 (d, 1H), 5.45 (br s, 2H), 2.02 (s, 3H).
f) A^-(5-(4-bromo-2-nitrophenylamino)-2',4'-difluorobiphenyl-3-yl)acetamide
A solution of N-(5-amino-2',4'-difluorobiphenyl-3-yl)acetamide (3.0 g, 11.44
mmol), 4-bromo-l-fluoro-2-nitrobenzene (2.52 g, 11.44 mmol, 1.0 eq.) and potassium
fluoride (0.663 g, 11.44 mmol, 1.0 eq.) in DMF was heated at 130 °C for 5 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the crude residue was
purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to
afford the title product in 45 % yield (2.4 g).
g) iV-(5-(2-amino-4-bromophenylamino)-2',4'-difluorobiphenyl-3-yl)acetamide

To a solution of A-(5-(4-bromo-2-nitrophenylamino)-2',4'-difluorobiphenyl-3-
yl)acetamide (3.2 g, 6.92 mmol) in THF (30 ml) were added a solution of ammonium
chloride (3.7 g, 69.22 mmol, 10 eq.) in water (15 ml) and zinc (4.53 g, 69.22 mmol, 10
eq.). The mixture was stirred at room temperature for 6 h and filtered. The filtrate was
diluted with water and extracted with ethyl acetate (3 * 100 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 87 % yield (2.6 g).
h)iV-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)-
acetamide
A mixture of Af-(5-(2-amino-4-bromophenylamino)-2',4'-difluorobiphenyl-3-
yl)acetamide (2.6 g, 6.01 mmol) and formic acid (10 ml) was heated at 100 °C for 30
min. The formic acid was distilled off under reduced pressure and the crude was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 60 % yield (1.6 g). 1H NMR (300 MHz, DMSO-d6): δ 10.41
(s, 1H), 8.72 (s, 1H), 8.02 (d, 2H), 7.82 (s, 1H), 7.75-7.66 (m, 2H), 7.53-7.41 (m, 3 H),
7.27 (m, 1H), 2.11 (s, 3H).
i)N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)biphenyl-3-yl)acetamide
A solution of N-(5-(5-bromo-1 H-benzo[d]imidazol-1 -yl)-2',4'-difluorobiphenyl-
3-yl)acetamide (1.5 g, 3.39 mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-
zole (0.847 g, 4.07 mmol, 1.2 eq.) was added and the mixture was degassed for another
5 min. Pd(dppf)Cl2 (0.553g, 0.678 mmol, 0.2 eq.) and aqueous sodium carbonate (1.08
g, 10.18 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed
for 5 min and then heated at 90 °C for 3 h. The reaction mixture was quenched with
water and extracted with ethyl acetate (3><50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off

under reduced pressure and the crude residue was purified by column chromatography
(60-120 silica gel, 80 % ethyl acetate in hexane) to afford the title product in 67 % yield
(1.0 g). 1H NMR (300 MHz, DMSO-d6): δ 10.4 (s, 1H), 8.64 (s, 1H), 8.2 (1H, s), 8.07
(s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.8-7.68 (m, 2 H), 7.6-7.45 (m, 4 H), 7.27 (t, 1H),
3.88 (s, 3H), 2.12 (s, 3H); LC-MS (ESI): Calculated mass: 443.45; Observed mass:
444.1 [M+H]+(RT: 1.2 min).
Example 2.
A'-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl- 3 -yl)methanesulfonamide
a)2',4'-Difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3-amine
To a solution of N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo-
[d]imidazol-l-yl)biphenyl-3-yl)acetamide of Example 1 (1.0 g, 2.26 mmol) methanol
(10 ml) was added aqueous solution of NaOH (800 mg, 20 mmol, 8.9 eq.) and the
mixture was heated at 85 °C for 5 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 66 % yield (0.6 g). LC-MS (ESI): Calculated mass:
401.41; Observed mass: 402.1 [M+Hf (RT: 1.198 min).
b)7Y-(2',4,-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3 -yl)methanesulfonamide
To a solution of 2',4'-difmoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-amine (50 mg, 0.125 mmol) in DCM was added pyridine (20
mg, 0.249 mmol, 2.0 eq.) followed by methanesulfonyl chloride (17 mg, 0.15 mmol. 1.2
eq.). The mixture was stirred for 1 h, quenched with water and extracted with DCM (3 x
50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the crude

residue was purified by preparative HPLC to give the title product in 33 % yield (20
mg). 1H NMR (300 MHz, DMSO-d6): δ 10.26 (s, 1H), 8.66 (s, 1H), 8.2 (s, 1H), 7.98 (s,
1H), 7.94 (s, 1H), 7.75-7.67 (m, 2 H), 7.57 (t, 3 H), 7.45-7.43 (m, 2 H), 7.29-7.25 (m,
1H), 3.87 (s, 3H), 3.17 (s, 3H); LC-MS (ESI): Calculated mass: 479.5; Observed mass:
480.2 [M+H]+ (RT: 1.34 min).
Example 3.
N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3 -yl)ethanesulfonamide
The compound was prepared from the title compound of Example 1 using the
procedures described in Example 2. lU NMR (300 MHz, DMSO-d6): δ 10.29 (s, 1H),
8.84 (s, 1H), 8.22 (s, 1H), 7.99 (s, 1H), 7.96 (s, 1H), 7.78-7.62 (m, 3H), 7.57 (br s, 2H),
7.48-7.43 (m, 2H), 7.29-7.25 (m, 1H), 3.88 (s, 3H), 3.29 (quartet, 2H), 1.25 (t, 3H); LC-
MS (ESI): Calculated mass: 493.53; Observed mass: 494.2 [M+H]+ (RT: 1.41 min).
Example 4.
N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3-yl)propane-2-sulfonamide
The compound was prepared from the title compound of Example 1 using the
procedures described in Example 2. 1H NMR (300 MHz, DMSO-4): δ 10.29 (s, 1H),
8.81 (s, 1H), 8.22 (s, 1H), 7.99 (s, 1H), 7.95 (s, 1H), 7.75-7.56 (m, 5 H), 7.48-7.43 (m, 2
H), 7.27 (m, 1H), 3.88 (s, 3H), 3.48-3.44 (m, 1H), 1.3 (d, 6H); LC-MS (ESI): Calculated
mass: δ07.55; Observed mass: δ08.2 [M+H]+ (RT: 1.47 min).
Example 5.
N-(2',4'-difluoro-5-(5-(1-methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1-yl)-
biphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the title compound of Example 1 using the
procedures described in Example 2. 1H NMR (300 MHz, DMSO-d6): 3 10.29 (s, 1H),

8.88 (s, 1H), 8.23 (s, 1H), 8.0 (s, 1H), 7.96 (s, 1H), 7.76-7.64 (m, 3H), 7.6 (s, 2H), 7.5-
7.46 (m, 2H), 7.3-7.25 (m, 1H), 3.88 (s, 3H), 2.88-2.85 (m, 1H), 1.02-1.0 (m, 4H); LC-
MS (ESI): Calculated mass: δ05.54; Observed mass: δ06.1 [M+H]+ (RT: 1.517 min).
Example 6.
yV-(2',4'-difluoro-5-(5-(l -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-
biphenyl-3-yl)cyclopentanesulfonamide
The compound was prepared from the title compound of Example 1 using the
procedures described in Example 2. 1H NMR (300 MHz, DMSO-c?6): δ 10.25 (s, 1H),
8.96 (s, 1H), 8.24 (s, 1H), 8.0 (s, 1H), 7.97 (s, 1H), 7.77-7.66 (m, 3 H), 7.6-7.59 (m, 2
H), 7.49 (m, 1 H), 7.46-7.43 (m, 1H), 7.3-7.25 (m, 1H), 3.88 (s, 3H), 3.83-3.78 (m, 1H),
1.99-1.93 (m, 4H), 1.69-1.64 (m, 2H), 1.63-1.52 (m, 2H); LC-MS (ESI): Calculated
mass: δ33.59; Observed mass: δ34.3 [M+H]+ (RT: 1.57 min).
Example 7.
N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3-yl)benzenesulfonamide
The compound was prepared from the title compound of Example 1 using the
procedures described in Example 2. lH NMR (300 MHz, DMSO-de): δ 8.57 (s, 1H),
8.21 (s, 1H), 7.96-7.95 (m, 2H), 7.88-7.86 (m, 2H), 7.72-7.61 (m, 4 H), 7.57-7.55 (m, 2
H), 7.5 (br s, 1H), 7.45-7.32 (m, 4 H), 7.26-7.22 (m, 1H), 3.88 (s, 3H); LC-MS (ESI):
Calculated mass: δ41.57; Observed mass: δ42.1 [M+H]~(RT: 1.642 min).
Example 8.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-2',4'-difluorobiphenyl-3-yl)acetamide
A solution of A^-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-
3-yl)acetamide of Example 1(h) (7 g, 15.83 mmol) in 1,2-dimethoxyethane (200 ml)
was degassed by N2 bubbling for 5 min. Ar,N-dimethyl-2-(4-(4,4,5,5-tetramethyl-l,3,2-

dioxaborolan-2-yl)-lH-pyrazol-l-yl)ethanamine of Intermediate Example 1 (6.3 g, 23.74
mmol, 1.5 eq.) was added and the mixture was degassed for another 5 min. Pd(PPh3)4
(1.83 g, 1.583 mmol, 0.1 eq.) and aqueous sodium carbonate (5.03 g, 47.5 mmol, 3.0
eq.) were added sequentially and the mixture was further degassed for 5 min and then
heated at 100 °C for 12 h. The reaction mixture was quenched with water and extracted
with ethyl acetate (3 x 50 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the crude residue was purified by column chromatography (neutral
alumina, 80 % ethyl acetate in hexane) to give the title product in 19 % yield (1.5 g). H
NMR(300 MHz, DMSO-d6): δ; 10.45 (s, 1H), 8.8 (s, 1H), 8.35 (s, 1H), 8.15 (s, 2H),
8.05 (s, 1H), 7.6-7.7 (m, 4H), 7.4-7.55 (m, 2H), 7.2-7.3 (m, 1H), 4.56 (t, 2H), 3.65-3.63
(m, 2H), 2.85 (s, 611), 2.12 (s, 3H); LC-MS (ESI): Calculated mass: δ00.54; Observed
mass: δ01.2 [M+H]+ (RT: 0.277 min).
Example 9.
7Y-(5-(5 -(1 -(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -
yl)-2',4'-difluorobiphenyl-3-yl)methanesulfonamide
a) 5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-2',4'-difluorobiphenyl-3-amine
To a solution of 7Y-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-
benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)acetamide of Example 8 (1.5 g, 3.0
mmol) in ethanol (30 ml) was added aqueous solution of NaOH (1.5 g, 37.5 mmol, 12.5
eq.) and the mixture was heated at 100 °C for 4 h. The reaction mixture was quenched
with water and extracted with ethyl acetate (3 * 100 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure to afford the title product in 58 % yield (0.8 g).
b)A-(5-(5-(l-(2-(dimcthylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-
l-yl)-2',4'-difluorobiphenyl-3-yl)methanesulfonamide

To a solution of 5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo-
[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-amine (200 mg, 0.436 mmol) in DCM was
added pyridine (69 mg, 0.872 mmol, 2.0 eq.) followed by methanesulfonyl chloride (75
mg, 0.654 mmol, 1.5 eq.). The mixture was stirred for 1 h, quenched with water and
extracted with DCM (3 x 50 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the crude residue was purified by preparative HPLC to give the title
product in 13 % yield (30 mg). 1H NMR (300 MHz, DMSO-MSO-d6): δ 10.33 (s, 1H),
8.78 (s, 1H), 8.46 (s, 1H), 8.15 (s, 1H), 7.8-7.73 (m, 4H), 7.58-7.55 (m, 2H), 7.48-7.43
(m, 2H), 7.29-7.25 (m, 1H), 3.29 (quartet, 2H), 1.25 (t, 3H); LC-MS (ESI): Calculated
mass: 480.49; Observed mass: 481.1 [M+H]+ (RT: 1.517 min).
Example 25.
J¥-(2',4'-difluoro-5-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)-
propane-2-sulfonamide
The compound was prepared from the compound of Example 22 using the
procedures described in Example 23. 1H NMR (300 MHz, DMSO-4): 6 10.31 (s, 1H),
8.8 (s, 1H), 8.46 (s, 1H), 8.16 (s, 1H), 7.78 (d, 4H), 7.58 (m, 2H), 7.5-7.43 (m, 2H), 7.3-
7.25 (m, 1 H), 3.49-3.47 (m, 1H), 1.3 (d, 6H); LC-MS (ESI): Calculated mass: 495.41;
Observed mass: 496.1 [M+H]+ (RT: 1.66 min).
Example 26.
A*-(2',4'-difluoro-5-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)-
benzenesulfonamide
The compound was prepared from the compound of Example 22 using the
procedures described in Example 23. *H NMR (300 MHz, DMSO-cfe): δ 10.9 (s, 1H),
8.77 (s, 1H), 8.47 (s, 1H), 8.14 (s, 1H), 7.88 (d, 2H), 7.78-7.74 (m, 2H), 7.72-7.61 (m,

4H), 7.54 (s, 1H), 7.49-7.45 (m, 1H), 7.43-7.39 (m, 3H), 7.27-7.22 (m, 1H); LC-MS
(ESI): Calculated mass: δ28.53; Observed mass: δ29.1 [M+H]+ (RT: 1.641 min).
Example 27.
iV-(5-(5-(3,5-dimethylisoxazol-4-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-difluoro-
biphenyl-3-yl)acetamide
The compound was prepared from the compound of Example 1 (h) using the
procedures described in Example 1. 1H NMR (300 MHz, DMSO-d6): δ 12.15 (br s, 1H),
10.24 (s, 1H), 8.67 (s, 1H), 8.08 (s, 1H), 7.82 (s, 1H), 7.78-7.73 (m, 2H), 7.65 (s, 1H),
7.53 (s, 1H), 7.48-7.43 (m, 1H), 7.3-7.25 (m, 2H), 2.23 (s, 6H), 2.12 (s, 3H); LC-MS
(ESI): Calculated mass: 457.47; Observed mass: 458 [M+H]+ (RT: 0.75 min).
Example 28.
N-(5 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo [d] imidazol-1 -yl)-2',4'-difluorobiphenyl-3-
yl)acetamide
To a solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobi-
phenyl-3-yl)acetamide of Example 1(h) (5 g, 11.31 mmol) in DMF (20 ml) were added
pyrazole (5 g, 73.49 mmol, 6.5 eq.), copper(I) oxide (4.86 g, 33.92 mmol, 3.0 eq.) and
cesium carbonate (14.73 g, 45.22 mmol, 4.0 eq.) and the mixture was heated at 90 °C for
48 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3
x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the crude
residue was purified by column chromatography (neutral alumina, 1 % methanol in
DCM) to give the title product in 49 % yield (2.4 g). *H NMR (300 MHz, DMSO-d6): δ
10.43 (s, 1H), 8.8 (s, 1H), 8.6 (d, 1H), 8.25 (s, 1H), 8.1 (s, 1H), 7.9-8.0 (m, 1H), 7.7-7.9
(m, 4H), 7.4-7.6 (m, 2H), 7.2-7.3 (m, 1H), 6.6 (m, 1H), 2.1 (s, 3H); LC-MS (ESI):
Calculated mass: 429.42; Observed mass: 430.4 [M+Hf (RT: 1.46 min).
Example 29.

A^-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-
yl)methanesulfonamide
a) 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-
amine
To a solution of iV-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-yl)acetamide of Example 28 (2.4 g, 5.59 mmol) in ethanol (40 ml) was
added aqueous solution of NaOH (2.4 g, 60 mmol, 10.7 eq.) and the mixture was heated
at 85 °C for 5 h. The reaction mixture was quenched with water and extracted with ethyl
acetate (3 x 100 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 69 % yield (1.5 g).
b) N-(5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',4'-difiuorobiphenyl-
3 -yl)methanesulfonamide
To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-amine (250 mg, 0.645 mmol) in DCM was added pyridine (102 mg,
1.29 mmol, 2.0 eq.) followed by methanesulfonyl chloride (100 mg, 0.877 mmol, 1.4
eq.). The mixture was stirred for 1 h, quenched with water and extracted with DCM (3 x
50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by preparative HPLC to give the title product in 33 % yield (100 mg). 1H
NMR (300 MHz, DMSO-d6): δ 10.31 (s, 1H), 8.85 (s, 1H), 8.62 (d, 1H), 8.25 (d, 2H),
7.95-7.92 (m, 1H), 7.84-7.77 (m, 3H), 7.62 (s, 1H), 7.58 (s, 1H), 7.51-7.44 (m, 2H),
7.33-7.27 (m, 1H), 3.19 (s, 3H); LC-MS (ESI): Calculated mass: 465.48; Observed
mass: 466.1 [M+H]+ (RT: 1.606 min).
Example 30.
N-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-
yl)ethanesulfonamide

The compound was prepared from the compound of Example 28 using the
procedures described in Example 29. 1HNMR (300 MHz, DMSO-d6): δ 10.3-10.4 (Br s,
1H), 8.75 (s, 1H), 8.6 (d,lH), 8.25(d, 1H), 7.9-7.95 (dd, 1H), 7.7-7.8 (m, 3H), 7.55 (m,
2H), 7.4-7.5 (m, 2H), 7.3 (m, 1H), 6.55 (m, 1H), 4.1 (q, 2H), 1.2-1.3 (t, 3H); LC-MS
(ESI): Calculated mass: 479.5; Observed mass: 480.1 [M+H]+ (RT: 1.641 min).
Example 31.
N-(5-(5-(l H-pyrazol-1 -yl)- lH-benzo[d] imidazol-1 -yl)-2',4'-difluorobiphenyl-3 -
yl)propane-2-sulfonamide
The compound was prepared from the compound of Example 28 using the
procedures described in Example 29. [HNMR (300 MHz, DMSO-o?6): δ 10.3 (s, 1H),
8.78 (s, 1H), 8.61 (d, 1H), 8.25 (d, 1H), 7.94 (dd, 1H), 7.78-7.75 (m, 3H), 7.61-7.57 (m,
2H), 7.5-7.48 (m, 1H), 7.46-7.43 (m, 1H), 7.29-7.25 (m, 1H), 6.6 (s, 1H), 3.5-3.46 (m,
1H), 1.31 (d, 6H); LC-MS (ESI): Calculated mass: 493.53; Observed mass: 494.1
[M+H]+(RT; 1.61 min).
Example 32.
N-(5 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-2',4'-difluorobiphenyl-3 -
yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 28 using the
procedures described in Example 29. 1H NMR (300 MHz, DMSO-d6): δ 10.34 (s, 1H),
9.0 (s, 1H), 8.64 (d, 1H), 8.27 (d, 1H), 7.99 (dd, 1H), 7.85-7.76 (m, 3H), 7.65-7.62 (m,
2H), 7.54-7.45 (m, 2H), 7.33-7.27 (m, 1H), 6.59-6.57 (m, 1H), 2.95-2.93 (m, 1H), 1.04-
1.02 (m, 4H); LC-MS (ESI): Calculated mass: 491.51; Observed mass:492.1 [M+Hf
(RT: 1.659 min).
Example 33.
1 -(5 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',4'-difluorobiphenyl-3 -
yl)-3-(furan-2-ylmethyl)urea

To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-amine of Example 29(a) (250 mg, 0.645 mmol) in n-butanol was
added TEA (200 mg, 1.98 mmol, 3.05 eq.) followed by 2-(isocyanatomethyl) furan (160
mg, 1.3 mmol, 2.0 eq.). The mixture was stirred for 1 h, quenched with water and
extracted with ethylacetate (3 * 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 18
% yield (60 mg). JH NMR (300MHz, DMSO-d6): δ 9.07 (s, 1H), 8.84 (s, 1H), 8.61 (d,
1H), 8.24 (d, 1H), 7.96-7.93 (m, 2H), 7.84-7.71 (m, 3H), 7.64-7.6 (m, 2H), 7.46-7.41
(m, 2H), 7.27-7.23 (m, 1H), 6.82 (t, 1H), 6.58-6.56 (m, 1H), 6.41-6.4 (m, 1H), 6.28-6.27
(m, 1H), 4.32 (d, 2H); LC-MS (ESI): Calculated mass: δ10.49; Observed mass: δ11.1
[M+H]+(RT: 1.59 min).
Example 34.
yV-(5-(5-( 1 H-imidazol-1 -yl> 1 H-benzo [d] imidazol-1 -yl)-2',4'-difiuorobiphenyl-3 -
yl)acetamide
The compound was prepared from the compound of Example 1(h) using the
procedures described in Example 28. 1H NMR (300 MHz, DMSO-d6): δ; 10.44 (s, 1H),
8.86 (s, 1H), 8.29 (s, 2H), 8.14 (s, III), 7.92 (d, 2H), 7.79-7.71 (m, 4H), 7.55 (s, 1H),
7.47-7.43 (m, 1H), 7.29-7.26 (m, 1H), 2.1 (s, 3H); LC-MS (ESI): Calculated mass:
429.42; Observed mass:430.2 [M+H]+ (RT: 0.21 min).
Example 35.
A-(2',4'-difluoro-5-(4,5,6,7-tetrahydro-l1H-l,5'-bibenzo[d]imidazol-r-yl)bi-
phenyl-3-yl)acetamide
The compound was prepared from the compound of Example 1(h) using the
procedures described in Example 28. 1H NMR (300 MHz, CD3OD): δ 8.66 (s, 1H), 8.15
(t, 1H), 7.86-7.75 (m, 4H), 7.69-7.62 (m, 1H), 7.55 (d, 1H), 7.43 (dd, 1H), 7.18-7.1 (m,

2H), 2.67-2.57 (m, 4H), 2.2 (s, 3H), 1.91-1.85 (m, 4H); LC-MS (ESI): Calculated mass:
483.51; Observed mass: 484.2 [M+H]+ (RT: 0.632 min).
Example 36.
N-(5-(5-(l-cyclopentyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-yl)acetamide
A solution of iV-(5-(5-iodo-1 H-benzo[d]imidazol-1 -yl)-2',4'-difluorobiphenyl-3-
yl)acetamide of Example 17(c) (60 mg, 0.123 mmol) in 1,2-dimethoxyethane (10 ml)
was degassed by N2 bubbling for 5 min. l-cyclopentyl-4-(4,4,5,5-tetramethyl-l,3,2-
dioxaborolan-2-yl)-lH-pyrazole (35 mg, 0.135 mmol, 1.1 eq.) was added and the
mixture was degassed for another 5 min. Pd(dppf)Cl2 (20 mg, 0.025 mmol, 0.2 eq.) and
aqueous sodium carbonate (39 mg, 0.369 mmol, 3.0 eq.) were added sequentially and
the mixture was further degassed for 5 min and then heated at 100 °C overnight. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 25 % yield (15 mg). lR NMR
(300 MHz, DMSO-4): δ 10.4 (s, 1H), 8.63 (s, 1H), 8.30 (s, 1H), 8.07 (s, 1H), 8.02 (s,
1H), 7.95 (s, 1H), 7.8 (s, 1H), 7.78-7.76 (m, 2H), 7.63-7.61 (m, 1H), 7.51 (s, 1H), 7.45-
7.40 (m, 1H); 7.27 (dt, 1H), 4.73-4.69 (m, 1H), 2.12-2.01 (m, 5H), 2.01-1.96 (m, 2H),
1.85-1.81 (m, 2H), 1.69-1.66 (m, 2H); LC-MS (ESI): Calculated mass: 497.54;
Observed mass: 498.5 [M+H]+ (RT: 1.59 min).
Example 37.
N-(2',4'-difluoro-5 -(5 -(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)-1 H-benzo [d]-
imidazol-1 -yl)biphenyl-3-yl)acetamide
a) terr-butyl 4-(4-(l -(5-acetamido-2',4'-difluorobiphenyl-3-yl)-lH-benzo[d]-
imidazol-5 -yl)-1 H-pyrazol-1 -yl)piperidine-1 -carboxylate

A solution of A^-(5-(5-iodo-lH-benzo[d]imidazoi-l-yl)-2',4'-difluorobiphenyl-3-
yl)acetamide of Example 17(c) (150 mg, 0.306 mmol) in 1,2-dimethoxyefhane (5 ml)
was degassed by N2 bubbling for 5 min. tert-Buty\ 4-(4-(4,4,5,5-tetramethyl-l,3,2-di-
oxaborolan-2-yl)-lH-pyrazol-l-yl)piperidine-l-carboxylate of the Intermediate Example
5 (173 mg, 0.460 mmol, 1.5 eq.) was added and the mixture was degassed for another 5
min. Pd(PPh3)4 (50 mg, 0.0613 mmol, 0.2 eq.) and aqueous sodium carbonate (97 mg,
0.92 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5
min and then heated at 100 °C for 4 h. The reaction mixture was quenched with water
and extracted with ethyl acetate (3 x 20 ml). The combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure to afford the crude residue in 64 % yield (120 mg).
b) N-(2',4'-difluoro-5-(5-( 1 -(piperidin-4-yl)- lH-pyrazol-4-yl)-1 H-benzo[d]-
imidazol-1 -yl)biphenyl-3 -yl)acetamide
To a solution of ter/-Butyl 4-(4-(l-(5-acetamido-2',4'-difluorobiphenyl-3-yl)-lH-
benzo[d]imidazol-5-yl)-lH-pyrazol-l-yl)piperidine-l-carboxylate (120 mg, 0.2 mmol)
in 1,4-dioxane (8 ml) at 0 °C was added HC1 in dioxane and stirred at room temperature
for 30 min. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 24 % yield (25 mg). 1H NMR
(300 MHz, DMSO-Jg): δ 10.42 (s, III), 8.83 (br s, 1H), 8.70-8.68 (in, 1H), 8.45-8.43
(m, 1H) 8.34 (s, 1H), 8.14-8.13 (m, 1H), 8.06 (s, 2H), 7.78 (m, 1H), 7.76-7.72 (m, 2H),
7.68 (dd, 1H), 7.53 (s, 1H), 7.43-7.40 (m, 1H), 7.27 (dt, 1H), 4.55-4.45 (m, 1H), 3.17-
3.08 (m, 4H), 2.28-2.17 (m, 4H), 2.12 (s, 3H); LC-MS (ESI): Calculated mass: δ12.55;
Observed mass: δ13.2 [M+H]+ (RT: 0.22 min).
Example 38.
1 -(5 -(5 -(1 H-pyrazol-1 -yl> 1 H-benzo [djimidazol-1 -yl)-2',4'-difluorobiphenyl-3 -
yl)-3-cyclopentylurea
To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-amine of Example 29(a) (200 mg, 0.52 mmol) in n-butanol (10 ml)

was added triethylamine (157 mg, 1.56 mmol, 3 eq.) followed by isocyanatocyclo-
pentane (115 mg, 1.3 mmol, 1.04 eq.). The mixture was stirred for 1 h, quenched with
water and extracted with ethylacetate (3 * 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 15 % yield (39 mg). >H NMR (300MHZ, DMSO-d6): δ 8.83 (s, 1H), 8.72
(s, 1H), 8.60 (d, 1H), 8.23 (d, 1H), 7.90 (dd, 2H), 7.82-7.70 (m, 3H), 7.60 (d, 1H), 7.45
(dt, 1H), 7.34 (br s, 1H), 7.25 (dt, 1H), 6.57-6.56 (m, 1H), 6.46 (d, 1H), 4.0-3.93 (m,
1H), 1.87-1.82 (m,2H), 1.65-1.54 (m, 4H), 1.43-1.39 (m, 2H); LC-MS (ESI):
Calculated mass: 498.53; Observed mass: 499.3 [M+H]+ (RT: 1.66 min).
Example 39.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-2',4'-difluorobiphenyl-3-yl)methanesulfonamide
a)5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-2',4'-difiuorobiphenyl-3-amine
To a solution of 7V-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)acetamide of Example 20 (450 mg,
0.9 mmol) in ethanol (10 ml) was added aqueous solution of NaOH (450 mg, 11.25
mmol, 12.5 eq.) and the mixture was heated at 85 °C for 2 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 77 % yield (0.32 g).
b)N-(5-(5-(l-(2-(dimethyiamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-2',4'-difluorobiphenyl-3-yl)methanesulfonamide
To a solution of 5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-3-amine (80 mg, 0.174 mmol) in DCM
(10 ml) was added pyridine (28 mg, 0.35 mmol, 2 eq.) followed by methanesulfonyl

chloride (22 mg, 0.19 mmol, 1.1 eq.). The mixture was stirred for 2 h, quenched with
water and extracted with DCM (3 >; 50 ml). The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 11
% yield (10 mg). 1HNMR (300 MHz, DMSO-d6): δ 10.32 (s, 1H), 8.79 (s, 1H), 8.73 (s,
1H), 8.27 (s, 1H), 7.92 (dd, 1H), 7.82-7.77 (m, 2H), 7.60 (d, 2H), 7.49-7.44 (m, 2H),
7.30-7.27 (m, 1H), 4.88 (t, 2H), 3.73 (m, 2H), 3.19 (s, 3H), 2.89 (s, 6H); LC-MS (ESI):
Calculated mass: δ37.58; Observed mass: δ38.2 [M+H]+ (RT: 0.243 min).
Example 40.
N-(5 -(5 -(1 -(2-(dimethylamino)ethyl)-1H-1,2,3 -triazol-4-yl)-1 H-benzo[d]-
imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)ethanesi]lfonamide
The compound was prepared from the compound of Example 20 using the
procedures described in Example 39. *H NMR (300 MHz, DMSO-d6): δ 10.37 (s, 1H),
8.85 (s, 1H), 8.73 (s, 1H), 8.28 (s, 1H), 8.83 (d, 1H), 7.82-7.76 (m, 2H), 7.59 (s, 2H),
7.48-7.47 (m, 2H), 7.29 (dt, 1H), 4.89-4.86 (m, 2H), 3.73 (m, 2H), 3.30 (quartet, 2H),
2.90 (s, 6H), 1.26 (t, 3H); LC-MS (ESI): Calculated mass: δ51.61; Observed mass: δ52.2 [M+H]+ (RT: 0.282 min).
Example 41.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)propane-2-sulfonamide
The compound was prepared from the compound of Example 20 using the
procedures described in Example 39. *H NMR (300 MHz, DMSO-4): δ 10.32 (s, 1H),
8.79 (s, 1H), 8.73 (s, 1H), 8.27 (s, 1H), 7.93 (d, 1H), 7.80-7.75 (m, 2H), 7.59 (d, 2H),
7.50-7.47 (m, 2H), 7.29 (dt, 1H), 4.88 (t, 2H), 3.74 (m, 2H), 3.50-3.46 (m, 1H), 2.89 (s,
6H), 1.31 (d, 6H); LC-MS (ESI): Calculated mass: δ65.64; Observed mass: δ66.2
[M+H]+ (RT: 0.402 min).
Example 42.

N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 20 using the
procedures described in Example 39. 1H NMR (400 MHz, CD3OD): δ 8.93 (s, 1H), 8.53
(s, 1H), 8.32 (s, 1H), 7.80 (d, 1H), 7.82 (d, 1H), 7.68-7.58 (m, 4H), 7.17-7.10 (m, 2H),
4.95 (t, 2H), 3.85 (t, 2H), 3.02 (s, 6H), 2.78-2.71 (m, 1H), 1.16-1.09 (m, 2H), 1.05-1.01
(m, 2H); LC-MS (ESI): Calculated mass: δ63.62; Observed mass: δ64.2 [M+H]+ (RT:
0.412 min).
Example 43.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)-2',4'-difluorobiphenyl-3-yl)benzenesulfonamide
The compound was prepared from the compound of Example 20 using the
procedures described in Example 39. ]H NMR (300 MHz, DMSO-^6): § 10.92 (s, 1H),
8.73 (d, 2H), 8.25 (s, 1H), 7.90-7.88 (m, 3H), 7.70-7.62 (m, 4H), 7.55-7.38 (m, 5H),
7.26-7.20 (m, 1H), 4.90-4.87 (m, 2H), 3.73 (t, 2H), 2.89 (s, 6H); LC-MS (ESI):
Calculated mass: δ99.65; Observed mass: 600.2 [M+H]+ (RT: 0.75 min).
Example 44.
N-(2',4'-difluoro-5-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)biphenyl-3 -yl)acetamide
A mixture of N-(5-(5-ethynyl-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-
3-yl)acetamide (0.5 g, 1.25 mmol) of Example 17(e), 4-azido-2-methylbutan-2-ol of
Intermediate Example 6 (0.16 g, 1.25 mmol, 1.0 eq.), sodium ascorbate (0.25 g, 1.25
mmol, 1.0 eq.) and copper sulfate pentahydrate (0.155 g, 0.62 mmol, 0.5 eq.) in CH2C12
(5 ml), DMSO (2 ml) and water (2 ml) was stirred for 12 h at room temperature. The
reaction mixture was quenched with water and the precipitate formed was filtered and
dried. The crude product was purified by preparative HPLC to give the title product in
62 % yield (0.4 g). lH NMR (300 MHz, DMSO-tf6): δ 10.43 (s, 1H), 8.86 (s, 1H), 8.70

(s, 1H), 8.25 (s, 1H), 8.09 (s, 1H), 7.93 (d, 1H), 7.84-7.81 (m, 3H), 7.55 (s, 1H), 7.50-
7.43 (m, 1H), 7.30-7.25 (m, 1H), 4.51-4.56 (m, 2H), 2.13 (s, 3H), 2.05-1.99 (t, 2H), 1.18
(s, 6H); LC-MS (ESI): Calculated mass: δ16.54; Observed mass: δ17.2 [M+H]+ (RT:
1.226 min).
Example 45.
N-(2',4'-difluoro-5-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d]imidazol-l-yl)biphenyl-3-yl)methanesulfonamide
a)4-(4-(l-(5-amino-2',4'-difluorobiphenyl-3-yl)-lH-benzo[d]imidazol-5-yl)-lH-
l,2,3-triazol-l-yl)-2-methylbutan-2-ol
To a solution of N-(2',4'-difluoro-5-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-
triazol-4-yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)acetamide of Example 44 (400
mg, 0.77 mmol) in ethanol (20 ml) was added aqueous solution of NaOH (385 mg, 9.63
mmol, 12.5 eq.) and the mixture was heated at 90 °C for 3 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 38 % yield (140 mg).
b)N-(2',4'-difluoro-5-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-triazol-4-yl)-
1 H-benzo [d]imidazol-1 -yl)biphenyl-3 -yl)methanesulfonamide
To a solution of 4-(4-(l-(5-amino-2',4'-difluorobiphenyl-3-yl)-lH-benzo[d]-
imidazol-5-yl)-lH-l,2,3-triazol-l-yl)-2-methylbutan-2-ol (70 mg, 0.15 mmol) in DCM
(10 ml) was added pyridine (24 mg, 0.3 mmol, 2 eq.) followed by methanesulfonyl
chloride (19 mg, 0.165 mmol, 1.1 eq.). The mixture was stirred for 2 h, quenched with
water and extracted with DCM (3 x 50 ml). The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in
1.2 % yield (1 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.30 (s, 1H), 8.83 (s, 1H), 8.30
(s, 1H), 8.25 (s, 1H), 7.92 (d, 1H), 7.82-7.80 (m, 2H), 7.60 (d, 2H), 7.47 (s, 2H), 7.29-

7.21 (m, 1H), 4.49 (m, 2H), 3.19 (s, 3H), 2.02 (m, 2H), 1.18 (s, 6H); LC-MS (ESI):
Calculated mass: δ52.60; Observed mass: δ53.1 [M+H]+ (RT: 1.352min).
Example 46.
N-(2',4'-difluoro-5 -(5-( 1 -(3 -hydroxy-3-methylbutyl)-1H-1,2,3 -triazol-4-yl)-1H-
benzo[d]imidazol-l-yl)biphenyl-3-yl)ethanesulfonamide
The compound was prepared from the compound of Example 44 using the
procedures described in Example 45. 1H NMR (300 MHz, DMSO-cfe): δ 10.34 (s, 1H),
8.87 (s, 1H), 8.70 (s, 1H), 8.25 (s, 1H), 7.93 (dd, 1H), 7.84-7.80 (m, 2H), 7.59 (s, 2H),
7.49-7.44 (m, 2H), 7.29 (dt, 1H), 4.51-4.47 (m, 2H), 3.30 (quartet, 2H), 2.04-2.00 (m,
2H), 1.26 (t, 3H), 1.16 (s, 6H); LC-MS (ESI): Calculated mass: δ66.62; Observed mass: δ67.2 [M+H]+ (RT: 1.42 min).
Example 47.
N-(2',4'-difluoro-5 -(5 -(1 -(3 -hydroxy-3-methylbutyl)-1H-1,2,3-triazol-4-yl)-1H-
benzo[d]imidazol-1 -yl)biphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 44 using the
procedures described in Example 45. 1H NMR (400 MHz, CD3OD): δ 9.09 (s, 1H), 8.47
(s, 1H), 8.30 (s, 1H), 8.0 (d, 1H), 7.83 (d, 1H), 7.69-7.60 (m, 4H), 7.17-7.10 (m, 2H),
4.62-4.58 (m,2H), 2.78-2.69 (m, 1H), 2.17-2.13 (m,2H), 1.29-1.15 (m, 8H), 1.10-1.02
(m, 2H); LC-MS (ESI): Calculated mass: δ78.63; Observed mass: δ79.2 [M+H]+ (RT:
1.449 min).
Example 48.
N-(2*,4'-difluoro-5 -(5 -(1 -(2-morpholinoethyl)-1H-1,2,3-triazol-4-yl)-1H-
benzo[d]imidazol-1 -yl)biphenyl-3-yl)methanesulfonamide
a)2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d]imidazol-l-yl)biphenyl-3-amine

To a solution of iV-(2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-
4-yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)acetamide of Example 21 (1 g, 1.9
mmol) in ethanol (15 ml) was added aqueous solution of NaOH (0.95 g, 23.8 mmol,
12.5 eq.) and the mixture was heated at 90 °C for 4 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3*50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 63 % yield (600 mg).
b)N-(2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d] imidazol-1 -yl)biphenyl-3 -yl)methanesulfonamide
To a solution of 2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-4-
yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-amine (80 mg, 0.159 mmol) in DCM (10 ml)
was added pyridine (25 mg, 0.318 mmol, 2 eq.) followed by methanesulfonyl chloride
(21 mg, 0.191 mmol, 1.2 eq.). The mixture was stirred for 2 h, quenched with water and
extracted with DCM (3 * 50 ml). The solvent was distilled off under reduced pressure
and the residue was purified by preparative HPLC to give the title product in 13 % yield
(12 mg). 1HNMR(300 MHZ, DMSO-d6): δ 10.32 (s, 1H), 8.80 (s, 1H), 8.73 (s, 1H),
8.28 (s, 1H), 7.94-7.92 (d, 1H), 7.82-7.72 (m, 2H), 7.60 (d, 2H), 7.46-7.40 (m, 2H), 7.27
(dt, 1H), 4.89 (m, 2H), 3.96-3.94 (m, 6H), 3.77 (m, 4H), 3.19 (s, 3H); LC-MS (ESI):
Calculated mass: δ79.62; Observed mass: δ80.2 [M+H]+ (RT: 0.29 min).
Example 49.
N-(2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)bipheny 1-3 -yl)ethanesulfonamide
The compound was prepared from the compound of Example 21 using the
procedures described in Example 48. *H NMR (300 MHz, DMSO-d6): δ 10.41 (s, 1H),
8.83 (s, 1H), 8.80 (s, 1H), 8.32 (s, 1H), 7.97 (d, 1H), 7.85-7.80 (m, 2H), 7.63 (s, 2H),
7.52-7.50 (m, 2H), 7.33 (d, 1H), 4.93 (m, 2H), 4.0 (m, 6H), 3.70 (m, 4H), 3.34 (quartet,
2H), 1.30 (t, 3H); LC-MS (ESI): Calculated mass: δ93.65; Observed mass: δ94.2
[M+H]+ (RT: 0.36 min).

Example 50.
N-(2',4'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-l,2,3-triazol-4-yl)-lH-
benzo[d]imidazol-l-yl)biphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 21 using the
procedures described in Example 48. 1H NMR (300 MHz, DMSO-tf6): δ 10.9 (s, 1H),
8.73 (s, 1H), 8.62 (s, 1H), 8.22 (s, 1H), 7.9-7.87 (m, 3H), 7.71-7.62 (m, 4H), 7.55 (s,
1H), 7.47-7.39 (m, 4H), 7.28-7.24 (m, 1H), 4.12 (s, 3H); LC-MS (ESI): Calculated
mass: 605.6; Observed mass: 606.2 [M+H]+ (RT: 0.367 min).
Example 51.
N-(5 -(5-( 1 -cyclopentyl-1H-1,2,3 -triazol-4-yl)-1 H-benzo [djimidazol-1 -yl)-2',4'-
difluorobiphenyl-3-yl)acetamide
A solution of N-(5-(5-ethynyl-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-
3-yl)acetamide of Example 17(e) (100 mg, 0.258 mmol) in dry DMF (10 ml) in a sealed
tube was purged with N2 for 20 min, followed by the addition of azidocyclopentane of
Intermediate Example 7 (34 mg, 0.3 mmol, 1.2 eq.) and copper iodide (5 mg, 0.0258
mmol, 0.1 eq.) and stirred at 90 °C for 12 h. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 14
% yield (18 mg). 1H NMR (400 MHz, CD3OD): δ 8.55 (s, 1H), 8.43 (s, 1H), 8.36 (s,
1H), 8.23 (br s, 1H), 8.10 (s, 1H), 7.92-7.88 (m, 1H), 7.74 (d, 2H), 7.68-7.61 (m, 1H),
7.52 (s, 1H), 7.15-7.09 (m, 1H), 5.09-5.03 (m, 1H), 2.35-2.30 (m, 2H), 2.19-2.12 (m,
5H), 1.96-1.90 (m, 4H); LC-MS (ESI): Calculated mass: 498.53; Observed mass: 499.2
[M+H]+(RT: 1.55 min).
Example 52.
N-(5 -(5 -(1 -(cyclobutylmethyl)-1H-1,2,3-triazol-4-yl)-1 H-benzo [d] imidazol-1 -
yl)-2',4'-difluorobiphenyl-3-yl)acetamide

The compound was prepared from the compound of Example 17(e) using the
compound of Intermediate Example 8 and the procedure described in Example 51. H
NMR (300 MHz, DMSO-d6): δ 10.34 (s, III), 8.13 (s, 1H), 8.61 (s, 1H), 8.24 (s, 1H),
8.07 (s, 1H), 7.92-7.90 (d, 1H), 7.82-7.71 (m, 3H), 7.52 (s, 1H), 7.42 (m, 1H), 7.24-7.20
(m, 1H), 4.42 (d, 2H), 2.10 (s, 3H), 2.05 (m, 3H), 1.90-1.83 (m, 4H); LC-MS (ESI):
Calculated mass: 498.53; Observed mass: 499.2 [M+H]+ (RT: 1.55 min).
Example 53.
yV-(4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)bi-
phenyl-3 -yl)acetamide
a) iV-(4'-fluoro-5-nitrobiphenyl-3-yl)acetamide
A solution of N-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (10.0 g, 38.6
mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. 4-
Fluorophenylboronic acid (6.48 g, 46.3 mmol, 1.2 eq.) was added and the mixture was
degassed for another 5 min. Pd(dppf)Cl2 (3.15 g, 3.86 mmol, 0.1 eq.) and aqueous
sodium carbonate (12.28 g, 115.8 mmol, 3.0 eq.) were added sequentially and the
mixture was further degassed for 5 min and then heated at 100 °C for 4 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 150 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 30 % ethyl acetate in hexane) to give the
title product in 86 % yield (9.1 g). 1H NMR (300 MHz, DMSO-4): δ 10.53 (s, 1H),
8.57 (t, 1H), 8.17 (s, 1H), 8.09 (t, 1H), 7.86-7.74 (m, 2H), 7.41 (t, 2H), 7.15 (t, 1H), 2.13
(s, 311); LC-MS (ESI): Calculated mass: 274.25; Observed mass: 274.8 [M+H]+ (RT:
1.52 min).
b)N-(5-amino-4'-fluorobiphenyl-3-yl)acetamide
To a solution of N-(4'-fluoro-5-nitrobiphenyl-3-yl)acetamide (11.0 g, 40.1 mmol)
in methanol (30 ml) and ethyl acetate (15 ml) was added 10 % Pd/C (3.0 g, 0.3 eq.) and

the reaction vessel was purged with nitrogen gas for 5 min. The reaction mixture was
then hydrogenated with H2 balloon for a period of 12 h. The mixture was filtered
through a pad of celite and the filtrate was concentrated under reduced pressure to afford
the title compound in 92 % yield (9.0 g). 1H NMR (300 MHz, DMSO-^): δ 9.73 (s,
1H), 8.11 (s, 1H), 7.53-7.48 (m, 2H), 7.26 (t, 1H), 6.94-6.92 (m, 2H), 6.47 (s, 1H), 5.22
(s, 2H), 2.02 (s, 3H); LC-MS (ESI): Calculated mass: 244.26; Observed mass: 245.1
[M+H]+(RT: 0.312 min).
c)yV-(5-(4-bromo-2-nitrophenylamino)-4'-fluorobiphenyl-3-yl)acetamide
A solution of iV-(5-amino-4'-fluorobiphenyl-3-yl)acetamide (9.0 g, 36.85 mmol),
4-bromo-l-fluoro-2-nitrobenzene (8.11 g, 36.85 mmol, 1.0 eq.) and potassium fluoride
(2.14 g, 36.85 mmol, 1.0 eq.) in DMF was heated at 100 °C for 12 h and subsequently
quenched by the addition of water. The precipitate formed was filtered, washed with
cold water and hexane and dried under high vacuum to give the product as orange solid
in 92 % yield (15.0 g). 1HNMR (300 MHz, DMSO-d6): δ 10.14 (s, 1H), 9.45 (s, 1H),
8.25 (d, 1H), 7.69-7.62 (m, 5H), 7.35-7.24 (m, 4H), 2.07 (s, 3H); LC-MS (ESI):
Calculated mass: 444.25; Observed mass: 446.1 [M+H]+ (RT: 1.84 min).
d) N-(5-(2-amino-4-bromophenylamino)-4'-fluorobiphenyl-3-yl)acetamide
To a solution of Af-(5-(4-bromo-2-nitrophenylamino)-4'-fluorobiphenyl-3-yl)-
acetamide (15 g, 33.77 mmol) in THF (100 ml) were added a solution of ammonium
chloride (18.1 g, 337.7 mmol, 10 eq.) in water (15 ml) and zinc (22.1 g, 337.7 mmol, 10
eq.). The mixture was stirred at room temperature for 6 h and filtered. The filtrate was
diluted with water and extracted with ethyl acetate (3 x 100 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 93 % yield (13.0 g). *H
NMR (300 MHz, DMSO-d6): δ 9.84 (1H, s), 7.53-7.49 (m, 3H), 7.31-7.25 (m, 4H),
6.98-6.91 (m, 2H), 6.88-6.62 (m, 2H), 5.11 (s, 2H), 2.01 (s, 3H); LC-MS (ESI):
Calculated mass: 414.27; Observed mass: 416 [M+H]+ (RT: 1.73 min).

e)N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-fluorobiphenyl-3-yl)acetamide
A mixture of iV-(5-(2-amino-4-bromophenylamino)-2',4'-difluorobiphenyl-3-yl)-
acetamide (13.0 g, 31.38 mmol) and formic acid (20 ml) was heated at 100°C for 30
min. The formic acid was distilled off under reduced pressure and the crude was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 68 % yield (9.0 g). 1H NMR (300 MHz, DMSO-d6): § 10.38
(s, 1H), 8.77 (s, 1H), 8.14 (s, 1H), 8.02-7.97 (m, 1H), 7.9 (s, 1H), 7.82-7.77 (m, 2H),
7.7-7.67 (m, 1H), 7.63-7.62 (m, 1H), 7.54-7.5 (m, 1H), 7.36 (t, 2H), 2.12 (s, 3H); LC-
MS (ESI): Calculated mass: 424.27; Observed mass: 425.1 [M+H]+ (RT: 1.925 min).
f) N-(4'-fluoro-5-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-
biphenyl -3 -y l)acetamide
A solution of A-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-fluorobiphenyl-3-
yl)acetamide (1.3 g, 3.06 mmol) in 1,2-dimethoxyethane (30 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-
pyrazole (0.765 g, 3.68 mmol, 1.2 eq.) was added and the mixture was degassed for
another 5 min. Pd(PPh3)4 (0.707 g, 0.612 mmol, 0.2 eq.) and aqueous sodium carbonate
(0.973 g, 9.18 mmol, 3.0 eq.) were added sequentially and the mixture was further
degassed for 5 min and then heated at 90 °C for 3 h. The reaction mixture was quenched
with water and extracted with ethyl acetate (3 x 50 ml). The combined organic layer wras
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by column chromatography (60-120
silica gel, 80 % ethyl acetate in hexane) to give the title product in 46 % yield (0.6 g). 1H
NMR (300 MHz, DMSO-d6): δ 10.4 (s, 1H), 9.0 (s, 1H), 8.25 (s, 1H), 8.08 (s, 1H), 8.0
(d, 2H), 7.90 (s, 1H), 7.8 (m, 3H), 7.65 (m, 2H), 7.4 (t, 2H), 3.9 (s, 3H), 2.1 (s, 3H); LC-
MS (ESI): Calculated mass: 425.46; Observed mass: 425.9 [M+H]+ (RT: 1.13 min).
Example 54.

iV-(4'-lluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)biphenyl-3-yl)methanesulfonamide
a) 4'-fluoro-5-(5-(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)bi-
phenyl-3-amine
To a solution of A-(4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-yl)acetamide of Example 53 (0.6 g, 1.41 mmol) in ethanol (20
ml) was added aqueous solution of NaOH (451 mg, 11.3 mmol, 8.0 eq.) and the mixture
was heated at 85 °C for 4 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 44 % yield (0.24 g). LC-MS (ESI): Calculated
mass: 383.42; Observed mass: 384.1 [M+H]+ (RT: 1.004 min).
b) N-(4'-fluoro-5-(5-(l-methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-l-
yl)biphenyl-3-yl)methanesulfonamide
To a solution of 4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-amine (50 mg, 0.125 mmol) in DCM was added pyridine (20
mg, 0.249 mmol, 2.0 eq.) followed by methanesulfonyl chloride (17 mg, 0.15 mmol, 1.2
eq.). The mixture was stirred for 1 h, quenched with water and extracted with DCM (3 x
50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by preparative HPLC to give the product in 33 % yield (20 mg). 1H NMR
(300 MHz, DMSO-d6): δ 10.23 (br s, 1H), 8.71 (s, 1H), 7.97 (d, 2H), 7.85-7.8 (m, 2H),
7.69 (m, 2H), 7.61-7.58 (m, 2H), 7.52 (d, 2H), 7.38 (t, 2H), 3.89 (s, 3H), 3.19 (s, 3H);
LC-MS (ESI): Calculated mass: 461.51; Observed mass: 461.9 [M+H]+ (RT: 1.3 min).
Example 55.
,V-(4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)bi-
phenyl-3 -yl)ethanesulfonamide

The compound was prepared from the compound of Example 53 using the
procedures described in Example 54. 1H NMR (300 MHz, DMSO-4): δ 10.36 (br s,
1H), 9.35 (br s, 1H), 8.28 (s, 1H), 8.02 (d, 2H), 7.85-7.79 (m, 2H), 7.76-7.7 (m, 3H),
7.6-7.57 (m, 2H), 7.39 (t, 2H), 3.89 (s, 3H), 3.31 (quartet, 2H), 1.27 (t, 3H); LC-MS
(ESI): Calculated mass: 475.54; Observed mass: 475.9 [M+H]+ (RT: 1.38 min).
Example 56.
N-(4'-fluoro-5-(5-( 1-methyl-lH-pyrazol-4-yl)-1 H-benzo[d]imidazol-1-yl)-
biphenyl-3-yl)propane-2-sulfonamide
The compound was prepared from the compound of Example 53 using the
procedures described in Example 54. 1H NMR (300 MHz, DMSO-d6): δ 10.28 (br s,
1H), 8.92 (br s, 1H), 8.24 (s, 1H), 7.99 (d, 2H), 7.83-7.78 (m, 2H), 7.71-7.67 (m, 3H),
7.56 (d, 2H), 7.38 (t, 2H), 3.88 (s, 3H), 3.52-3.48 (m, 1H), 1.31 (d, 6H); LC-MS (ESI):
Calculated mass: 489.56; Observed mass: 490.2 [M+H]+ (RT: 1.46 min).
Example 57.
AA-(4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)bi-
phenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 53 using the
procedures described in Example 54. ]H NMR (300 MHz, DMSO-d6): δ 10.28 (s, 1H),
9.1 (br s, 1H), 8.26 (s, 1H), 8.01 (d, 2H), 7.84-7.81 (m, 2H), 7.74-7.71 (m, 3H), 7.59 (s,
2H), 7.39 (t, 2H), 3.89 (s, 3H), 2.91-2.89 (m, 1H), 1.03 (d, 4H); LC-MS (ESI):
Calculated mass: 487.55; Observed mass: 488.1 [M+H]+ (RT: 1.42 min).
Example 58.
l-cyclopentyl-3-(4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyI-3-yl)urea

To a solution of 4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-amine of Example 54(a) (100 mg, 0.261 mmol) inn-butanol
was added triethylamine (79 mg, 0.783 mmol, 3.0 eq.) followed by isocyanatocyclo-
pentane (58 mg, 0.522 mmol, 2.0 eq.). The mixture was stirred for 1 h, quenched with
water and extracted with ethylacetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 31 % yield (40 mg). 1H NMR (300 MHz, DMSO-d6): δ 8.84 (br s, 1H),
8.71 (s, 1H), 8.22 (s, 1H),7.99 (d, 2H),7.88 (s, 1H), 7.82-7.78 (m, 2H), 7.73 (d, 1H),
7.68-7.63 (m, 2H), 7.48 (s, 1H), 7.36 (t, 2H), 6.4 (d, 1H), 4.1-3.8 (m, 1H), 3.88 (s, 3H),
1.89-1.83 (m, 2H), 1.69-1.5 (m, 4H), 1.45-1.38 (m, 2H); LC-MS (ESI): Calculated
mass: 494.56; Observed mass: 494.8 [M+H]+ (RT: 1.51 min).
Example 59.
1 -(4'-fluoro-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)bi-
phenyl-3 -yl)-3 -(1 -methylpiperidin-4-yl)urea
To a solution of 4'-fluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-amine of Example 54(a) (50 mg, 0.13 mmol) in DCM at 0 °C
was added phosgene (20 % in toluene) (0.1 ml, 0.195 mmol, 1.5 eq.) and the mixture
was stirred for 15 min at 0 °C and 30 min at room temperature. l-Methylpiperidin-4-
amine (18 mg, 0.156 mmol, 1.2 eq.) was added and the mixture was stirred for 16 h. The
reaction mixture wras quenched by the addition of water and extracted with 8 %
methanol/DCM (3 x 50 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure
and the residue was purified by preparative HPLC to give the title product in 44 % yield
(30 mg). JH NMR (300 MHz, DMSO-d6): δ 8.48 (s, 1H), 7.98 (s, 1H), 7.89-7.85 (m,
4H), 7.72-7.55 (m, 6H), 7.39 (s, 1H), 7.2 (t, 2H), 3.94 (s, 3H), 3.89-3.84 (m, 1H), 3.42-
3.33 (m, 2H), 3.05-3.0 (m, 2H), 2.78 (s, 3H),2.17-2.13 (m, 2H), 1.85-1.81 (m, 2H); LC-
MS (ESI): Calculated mass: δ23.6; Observed mass: δ24 [M+H]+ (RT: 0.2 min).
Example 60.

1 -(4'-fluoro-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)bi-
phenyl-3-yl)-3-(furan-2-ylmethyl)urea
The compound was prepared from the compound of Example 54(a) using the
procedures described in Example 58. 1H NMR (300 MHz, CD3OD): δ 8 9.1 (s, 1H), 8.1
(s, 1H), 8.02 (s, 2H), 7.93 (s, 1H), 7.85-7.81 (m, 2H), 7.74-7.67 (m, 3H), 7.53 (d, 1H),
7.44 (d, 1H), 7.22 (t, 2H), 6.37-6.34 (m ,1H), 6.3-6.29 (m, 1H), 4.42 (s, 2H), 3.95 (s,
3H); LC-MS (ESI): Calculated mass: δ06.53; Observed mass: δ07.1 [M+H]+ (RT: 1.44
min).
Example 61.
1 -(4'-fluoro-5-(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)bi-
phenyl-3-yl)-3-((5-methylfuran-2-yl)methyl)urea
The compound was prepared from the compound of Example 54(a) using the
procedures described in Example 58. 1H NMR (300 MHz, CD3OD): S 9.51 (s, 1H), 8.1
(s, 1H), 8.02 (s, 2H), 7.93 (s, 1H), 7.85-7.73 (m, 4H), 7.65 (m, 1H), 7.53 (s, 1H), 7.22 (t,
2H), 6.2-6.14 (m ,1H), 5.9-5.81 (m, 1H), 4.38 (s, 2H), 3.95 (s, 3H), 2.26 (s, 3H); LC-MS
(ESI): Calculated mass: δ20.56; Observed mass: δ21.1 [M+H]+(RT: 1.51 min).
Example 62.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-4'-fluorobiphenyl-3-yl)acetamide
The compound was prepared from the compound of Example 53(e) using the
procedures described in Example 53. 1H NMR (300 MHz, DMSO-4): δ 10.42 (s, 1H),
8.98 (s, 1H), 8.37 (s, 1H), 8.14-8.06 (m, 3H), 7.85-7.75 (m, 4H), 7.68-7.66 (m, 2H),
7.38 (t, 2H), 4.57 (t, 2H), 3.65-3.63 (m, 2H), 2.85 (d, 6H), 2.13 (s, 3H); LC-MS (ESI):
Calculated mass: 482.55; Observed mass: 483.1 [M+H]+ (RT: 0.19 min).
Example 63.

N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-4'-fluorobiphenyl-3-yl)methanesulfonamide
The compound was prepared from the compound of Example 62 using the
procedures described in Example 54. lH NMR (300 MHz, DMSO-d6): δ 10.27 (s, 1H),
8.87 (s, 1H), 8.37 (s, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.84-7.8 (m, 2H), 7.76-7.64 (m,
3H), 7.55-7.52 (m, 2H), 7.38 (t, 2H), 4.57 (t, 2H), 3.65-3.62 (m, 2H), 3.19 (s, 3H), 2.86
(d, 6H); LC-MS (ESI): Calculated mass: δ18.61; Observed mass: δ19 [M+H]+ (RT: 0.22
min).
Example 64.
A-(5-(5-( 1 -(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -
yl)-4'-fluorobiphenyl-3-yl)ethanesulfonamide
The compound was prepared from the compound of Example 62 using the
procedures described in Example 54. lU NMR (300 MHz, DMSO-d6): δ 10.29 (s, 1H),
8.77 (s, 1H), 8.35 (s, 1H), 8.13 (s, 1H), 8.06 (s, 1H), 7.83-7.78 (m, 2H), 7.72-7.63 (m,
3H), 7.54-7.51 (m, 2H), 7.38 (t, 2H), 4.57 (t, 2H), .65-3.62 (m, 2H), 3.3 (quartet, 2H),
2.86 (d, 6H), 1.27 (t, 3H); LC-MS (ESI): Calculated mass: δ32.63; Observed mass: δ33
[M+H]+ (RT: 0.25 min).
Example 65.
N-(5-(5-(1-(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1-
yl)-4'-fluorobiphenyl-3-yl)propane-2-sulfonamide
The compound was prepared from the compound of Example 62 using the
procedures described in Example 54. 'fl NMR (300 MHz, DMSO-d6): δ 10.27 (s, 1H),
8.82 (s 1H), 8.36 (s, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.83-7.79 (m, 2H), 7.71-7.65 (m,
3H), 7.56-7.53 (m, 2H), 7.38 (t, 2H), 4.57 (t, 2H), 3.67-3.64 (m, 2H), 3.52-3.49 (m, 1H),
2.85 (d, 6H), 1.32 (d, 6H); LC-MS (ESI): Calculated mass: δ46.66; Observed mass: δ47.2 [M+H]+ (RT: 0.507 min).

Example 66.
N-(5-(5-(l -(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -
yl)-4'-fluorobiphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 62 using the
procedures described in Example 54. 1H NMR (300 MHz, DMSO-d6): δ 10.26 (s, 1H),
8.84 (s, 1H), 8.36 (s, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.82-7.79 (m, 2H), 7.73-7.67 (m,
3H), 7.56 (d, 2H), 7.39 (t, 2H), 4.57 (t, 2H), 3.65-3.62 (m, 2H), 2.9-2.87 (m, 1H), 2.86
(d, 6H), 1.02 (d, 4H); LC-MS (ESI): Calculated mass: δ44.64; Observed mass: δ46.2
[M+H]+ (RT: 0.401 min).
Example 67.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-4'-fluorobiphenyl-3-yl)benzenesulfonamide
The compound was prepared from the compound of Example 62 using the
procedures described in Example 54. 1H NMR (300 MHz, DMSO-4): δ 10.9 (s, 1H),
8.78 (s, 1H), 8.37 (s, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.89 (d, 2H), 7.72-7.68 (m, 3H),
7.66-7.61 (m, 4H), 7.41-7.33 (in, 5H), 4.57 (t, 2H), 3.66-3.63 (m, 2H), 2.85 (d, 6H); LC-
MS (ESI): Calculated mass: δ80.68; Observed mass: δ81.1 [M+H]+ (RT: 0.781 min).
Example 68.
1 -cyclopentyl-3 -(5 -(5 -(1 -(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-1H-
benzo[d]imidazol-l-yl)-4'-fluorobiphenyl-3-yl)urea
The compound was prepared from the compound of Example 62 using the
procedures described in Example 58. 1H NMR (300 MHz, DMSO-d6): δ 9.33 (br s, 1H),
8.87 (s, 1H), 8.76 (s, 1H), 8.36 (s, 1H), 8.14 (s, 1H), 8.05 (s, 1H), 7.39 (m, 1H), 7.82-
7.75 (m, 3H), 7.68-7.6 (m, 2H), 7.48 (m, 1H), 7.36 (t, 2H), 4.57 (t, 2H), 3.99-3.97 (m,
1H), 3.65-3.62 (m, 2H), 2.86 (d, 6H), 1.89-1.82 (m, 2H), 1.7-1.53 (m, 4H), 1.45-1.37
(m, 2H); LC-MS (ESI): Calculated mass: δ51.66; Observed mass: δ52.2 [M+H]+ (RT:
0.61 min).

Example 69.
N-(4'-fluoro-5 -(5 -(6-methoxypyridin-3 -yl> 1 H-benzo [d] imidazol-1 -yl)biphenyl-
3-yl)acetamide
The compound was prepared using the procedures described in Example 53. H
NMR (300 MHz, DMSO~d6): δ 10.41 (s, 1H), 8.96 (s, 1H), 8.58 (d, 1H), 8.15-8.07 (m,
3H), 7.91-7.89 (m, 1H), 7.85-7.79 (m, 3H), 7.74-7.67 (m, 2H), 7.38 (t, 2H), 6.95 (d,
1H), 3.92 (s, 3H), 2.14 (s, 3H); LC-MS (ESI): Calculated mass: 452.48; Observed mass:
453.1 [M+H]+(RT: 1.571 min).
Example 70.
N-(5 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-4'-fluorobiphenyl-3-yl)-
acetamide
To a solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-fluorobiphenyl-3-
yl)acetamide of Example 53(e) (1.0 g, 2.36 mmol) in DMF (5 ml) were added pyrazole
(1.0 mg, 14.87 mmol, 6.3 eq.), copper(I) oxide (1.0 g, 7.08 mmol, 3.0 eq.) and cesium
carbonate (3.0 g, 9.204 mmol, 3.9 eq.) and the mixture was heated at 90 °C for 48 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 62 % yield (0.6 g). [H NMR
(300 MHz, DMSO-c4): δ 10.39 (s, 1H), 8.8 (s, 1H), 8.6 (d, 1H), 8.24 (d, 1H), 8.02 (s,
1H), 7.93-7.9 (m, 2H), 7.82-7.56 (m, 4H), 7.65 (d, 1H), 7.37 (t, 2H), 6.56 (t, 1H), 2.13
(s, 3H); LC-MS (ESI): Calculated mass: 411.43; Observed mass: 412.3 [M+H]+ (RT:
1.43 min).
Example 71.
A-(5-(5-(lH-p>Tazol-l-yl)-lH-benzo[d]imidazol-l-yl)-4'-fluorobiphenyl-3-yl)-
methanesulfonamide

a) 5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-4'-fluorobiphenyl-3-amine
To a solution of A-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-4'-fluoro-
biphenyl-3-yl)acetamide of Example 70 (0.6 g, 1.46 mmol) in ethanol (40 ml) was
added aqueous solution of NaOH (1.0 g, 25 mmol, 17.1 eq.) and the mixture was heated
at 85 °C for 5 h. The reaction mixture was quenched with water and extracted with ethyl
acetate (3 x 100 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 84 % yield (0.45 g).
b) N-(5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-4'-fluorobiphenyl-3 -
yl)methanesulfonamide
To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-4'-fluoro-
biphenyl-3-amine (150 mg, 0.406 mmol) in DCM was added pyridine (0.5 ml, 6.21
mmol, 15.3 eq.) followed by methanesulfonyl chloride (70 mg, 0.609 mmol, 1.5 eq.).
The mixture was stirred for 1 h, quenched with water and extracted with DCM (3 * 50
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 17 % yield (30 mg). *H NMR
(300 MHz, DMSO-de): 6 10.23 (s, 1H), 8.82 (s, 1H), 8.6 (d, 1H), 8.24 (d, 1H), 7.92 (dd,
1H), 7.85-7.8 (m, 3H), 7.76-7.71 (m, 2H), 7.54-7.53 (m, 2H), 7.38 (t, 2H), 6.56 (t, 1H),
3.19 (s, 3H); LC-MS (ESI): Calculated mass: 447.48; Observed mass: 449.1 [M+H]+
(RT: 1.575 min).
Example 72.
N-(5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-4'-fluorobiphenyl-3 -yl)-
ethanesulfonamide
The compound was prepared from the compound of Example 70 using the
procedures described in Example 71. 1H NMR (300 MHz, DMSO-c?5): S 10.3 (s, 1H),
8.81 (s, 1H), 8.6 (d, 1H), 8.24 (s, 1H), 7.93 (dd, 1H), 7.84-7.76 (m, 4H), 7.7-7.69 (m,

1H), 7.55-7.53 (m, 2H), 7.4-7.36 (m, 2H), 6.57-6.56 (m, 1H), 3.3 (quartet, 2H), 1.27 (t,
3H); LC-MS (ESI): Calculated mass: 461.51; Observed mass: 462.1 [M+H]+ (RT: 1.563
min).
Example 73.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)acetamide
a)N-[3-(5-Methyl-furan-2-yl)-5-nitro-phenyl]-acetamide
To a solution of 7Y-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (5 g,
19.23 mmol) in 1,2-dimethoxyethane (200 ml) were added 4,4,5,5-tetramethyl-2-(5-
methylfuran-2-yl)-l,3,2-dioxaborolane (5.9 g, 28.85 mmol), sodium carbonate (8.15 g,
76.92 mmol) and water (20 ml) and the mixture was degassed by N2 bubbling 15 min.
Pd(dppf)Cl2 (3.2 g, 3.846 mmol) was added and the mixture was heated at 100 °C for 2
h. The mixture was brought to room temperature and quenched by the addition of water
(100 ml). The organic phase was separated and the aqueous phase was extracted with
ethyl acetate (2 x 200 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure
and the residue was purified by flash column chromatography (40 % ethyl acetate in
hexanes) to afford the product in 80 % yield (4.0 g). lH NMR (300 MHz, DMSO-d6): δ
10.45 (s, 1H), 8.4 (s, 1H), 8.2 (d, 2H), 7.1 (s, 1H), 6.2 (s, 1H), 2.4 (s, 3H), 2.15 (s, 3H),
Calculated mass: 260.25; Observed mass: 259.1 [M+H]+ (RT:1.578 min).
b)N-[3-Amino-5-(5-methyl-furan-2-yl)-phenyl]-acetamide
To a solution of iV-[3-Nitro-5-(5-methyl-furan-2-yl)-phenyl]-acetamide (4.0g,
15.384 mmol) in methanol (50 ml) was added 10 % palladium in carbon (500 mg) and
the mixture was stirred at room temperature under hydrogen atmosphere (balloon
pressure) for 6 h. The mixture was filtered over a pad of celite and washed with
methanol. The solvent was evaporated under reduced pressure to afford the title
compound in 95 % yield (3.3 g). *H NMR (300 MHz, DMSO-d6): δ 9.6 (s, 1H), 7.0 (d,

2H), 6.45 (d, 2H), 6.2 (s, 1H), 5.2 (s, 2H), 2.4 (s, 3H), 2.15 (s, 3H), Calculated mass:
230.26; Observed mass: 231.2 [M+H]+ (RT: 0.212 min).
c) A,-[3-(4-Bromo-2-nitro-phenylamino)-5-(5-methyl-fiiran-2-yl)-phenyl]-
acetamide
To a solution of N-[3-Amino-5-(5-methyl-furan-2-yl)-phenyl]acetamide (5 g,
22.73 mmol) in anhydrous DMF (25 ml), 4-bromo-l-fluoro-2-nitrobenzene (7.09 g, 27.3
mmol) and potassium fluoride (1.32g, 22.73 mmol) were added. The mixture was
stirred at 100 °C overnight. The mixture was brought to room temperature and DMF
was removed under reduced pressure. The residue was purified by flash column
chromatography (50 % ethyl acetate in hexanes) to give the title compound in 65 %
yield (6 g). 1HNMR (300 MHz, DMSO-d6): δ 10.2 (s, 1H), 9.6 (s, 1H), 8.2 (s, 1H), 7.7
(s, 2H), 7.5 (m, 1H), 7.30 (s, 1H), 7.2 (s, 1H), 6.7 (d, 1H), 2.9 (s, 1H), 2.33 (s, 3H), 2.15
(s, 3H), Calculated mass: 430.25; Observed mass: 432 [M+H]+ (RT: 1.85 min).
d) N-[3-(2-Amino-4-bromo-phenylamino)-5-(5-methyl-furan-2-yl)-phenyl]-
acetamide
To a solution of A^-[3-(4-Bromo-2-nitro-phenylamino)-5-(5-methyl-furan-2-yl)-
phenyl]-acetamide (6.0 g, 13.945 mmol) in ethanol (100 ml) were added iron powder
(500 mg) and 50 % aqueous calcium chloride solution (10 ml). The mixture was stirred
at 80 °C for 2 h and filtered through a celite pad. The celite pad was washed with ethyl
acetate (200 ml). The combined organic layer was washed with water, brine and dried
over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by flash column chromatography (20 % ethyl acetate in hexanes) to
get the title compound in 98 % yield (5.5 g). 1H NMR (300 MHz, DMSO-d6): δ 9.8 (s,
1H), 7.30 (d, 1H), 6.9 (m, 3H), 6.7 (m, 2H), 6.5 (d, 1H), 5.2 (s, 2H), 2.33 (s, 3H), 2.15
(s, 3H), Calculated mass: 400.27; Observed mass: 402 [M+H]+ (RT: 1.695 min).
e)A-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(5-methylfuran-2-yl)phenyl)-
acetamide

Formic acid (10 ml) was added to N-[3-(2-Amino-4-bromo-phenylamino)-5-(5-
methyl-furan-2-yl)-phenyl]acetamide (5 g, 12.49 mmol) at room temperature and then
the mixture was heated at 100 °C for 2 h. Formic acid was removed under reduced
pressure and the residue was purified by flash column chromatography (3 % methanol in
chloroform) to afford the title compound in 58 % yield (3.0 g). 1H NMR (300 MHz,
DMSO-4): § 10.3 (s, 1H), 8.7 (s, 1H), 8.0 (s, 1H), 7.9 (s, 2H), 7.6 (m, 2H), 7.5 (m, 1H),
7.0 (s, 1H), 6.3 (d, 1H), 2.33 (s, 3H), 2.15 (s, 3H), Calculated mass: 410.26; Observed
mass: 410.2 [M+H]+ (RT:1.616 min).
f)iV-(3-(5-(l-methyl-lH-pyTazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)acetamide
To a solution of N-[3-(5-Bromo-benzoimidazol-l-yl)-5-(5-methyl-furan-2-yl)-
phenyljacetamide (100 mg, 0.244 mmmol) in 1,2-dimethoxyethane (10 ml), 1-methyl-
4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.043 g, 0.341 mmol),
sodium carbonate (0.0755 g, 0.731 mmol) and water (2.0 ml) were added and the
mixture was degassed for 15 min. byN2 bubbling. Pd(PPh3)4 (0.0563 g, 0.0487 mmol)
was added and the mixture was heated at 100 °C for 2 h. The mixture was brought to
room temperature and quenched with water and extracted with ethyl acetate (3 * 50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to afford the title compound in 10 % yield (10 mg). 1H
NMR (300 MHz, DMSO-cfe): δ 10.2 (s, 1H), 8.6 (s, 1H), 8.4 (s, 1H), 7.8-8.1 (s, 4H),
7.6-7.7 (m, 4H), 7.0 (s, 1H), 6.3 (s, 1H), 3.9 (m, 1H), 2.4 (s, 3H), 2.15 (s, 4H),
Calculated mass: 411.46; Observed mass: 412.1 [M+H]+ (RT: 0.809 min).
Example 74.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)ethanesulfonamide

a)3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)aniline
A mixture of KOH (0.614 g,10.94 mmol) and N-{3-(5-Methyl-furan-2-yl)-5-[5-
(l-methyl-lH-pyrazol-4-yl)-benzoimidazol-l-yl]-phenyl}-acetamide of Example 73 (3.0
g,7.29mmol) in ethanol (5 ml) and water (2 ml) was heated at 60 °C for 2 h. The
mixture was diluted with ethyl acetate (100 ml) and was washed with water (50 ml) and
brine (25 ml). The organic phase was dried over sodium sulfate and concentrated under
vacuum and the residue was purified by column chromatography to afford the product in
92 % yield (2.5 g).
b) N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5 -(5-methyl-
furan-2-yl)phenyl)ethanesulfonamide
To a solution of 3-(5-methyl-furan-2-yl)-5-[5-(l-methyl-1 H-pyrazol-4-yl)-benzo-
imidazol-l-yl]phenylamine (0.1g,0.27 mmol) in pyridine (1 ml) and DCM (2 ml) was
added ethanesulfonyl chloride (0.1 ml) and the mixture was stirred at room temperature
for 12 h. The solvent was removed under reduced pressure and the crude was purified by
preparative HPLC to afford the title product in 24 % yield (0.03 g). 1H NMR (300 MHz,
CD3OD): δ 9.2 (s, 1H), 8.1 (s, 1H), 8.0 (s, 1H), 7.95 (s, 1H), 7.6-7.7 (m, 4H), 7.5 (s,
1H), 6.8 (d, 1H), 6.2 (s, 1H), 4.0 (s, 3H), 3.3 (m, 2H), 2.4 (s, 3H), 1.4 (t, 3H). LC-MS
(ESI): Calculated mass: 461.54; Observed mass: 462.1 [M+H]+ (RT: 1.315 min).
Example 75.
N-(3-(5-(l-methyl-lH-p>Tazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)propane-2-sulfonamide
The compound was prepared from the compound of Example 73 using the
procedures described in Example 74. *H NMR (300 MHz, CD3OD): δ ; 8.5 (s, 1H), 8.0
(s, 1H), 7.95 (s, 1H), 7.9 (s, 1H), 7.6-7.7 (m, 5H), 7.5 (s, 1H), 6.8 (d, 1H), 6.2 (s, 1H),
4.0 (s, 3H), 3.5 (m, 1H), 2.4 (s, 3H), 1.5 (d, 6H). LC-MS (ESI): Calculated mass:
475.56; Observed mass: 475.9 [M+H]+ (RT: 1.415 min).

Example 76.
N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(5-methyl-
furan-2-yl)phenyl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 73 using the
procedures described in Example 74. 1H NMR (300 MHz, CD3OD): δ 8.5 (s, 1H), 8.0
(s, 1H), 7.95 (s, 1H), 7.9 (s, 1H), 7.6-7.7 (m, 4H), 7.5 (s, 1H), 6.8 (d, 1H), 6.2 (s, 1H),
4.0 (s, 3H), 2.4 (s, 3H), 1.0-1.5 (m, 4H). LC-MS (ESI): Calculated mass: 473.55;
Observed mass: 474.0 [M+Hf (RT: 1.382 min).
Example 77.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)benzenesulfonamide
The compound was prepared from the compound of Example 73 using the
procedures described in Example 74. Yield 0.03g, (25%),1H NMR (300 MHz, CD3OD): δ ; 8.55 (s, 1H), 8.05 (s, 1H), 7.9 (m, 4H), 7.6-7.7 (m, 5H), 7.5 (s, 2H),7.4 (d, 1H), 7.2
(t, 1H), 6.8 (d, 1H), 6.2 (s, 1H), 4.0 (s, 3H), 2.4 (s, 3H). LC-MS (ESI): Calculated
mass: δ09.58; Observed mass: δ09.9 [M+H]+ (RT: 1.482 min).
Example 78.
1 -(furan-2-ylmethyl)-3 -(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-
l-yl)-5-(5-methylfuran-2-yl)phenyl)urea
To a solution of 3-(5-methyl-furan-2-yl)-5-[5-(l-methyl-lH-pyrazol-4-yl)-benzo-
imidazol-l-yl]-phenylamine of Example 74(a) (0.1 g, 0.271 mmol) in DCM (10 ml), at
0 °C, were added phosgene (0.04 g, 0.406 mmol) and furfuryl amine (0.029 g, 0.2977
mmol) sequentially. The mixture was heated at 60 °C for 2 h and the solvent was
evaporated under reduced pressure and the residue was purified by preparative HPLC to
give the title compound in 15 % yield (20 mg). 1H NMR (300 MHz, CD3OD): δ 9.6 (s,
1H), 8.2 (s, 1H), 8.0 (s, 1H), 7.95 (s, 2H), 7.6-7.7 (m, 5H), 7.7 (s, 1H), 7.6 (s, 1H), 6.4

(s, 1H), 6.3 (d, 1H), 6.2 (s, 1H), 4.5 (s, 2H), 4.0 (s, 3H), 2.4 (s, 3H), LC-MS (ESI):
Calculated mass: 492.53; Observed mass: 493.1 [M+H]+ (RT: 1.415 min).
Example 79.
1 -cyclopentyl-3 -(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-
(5-methylfuran-2-yl)phenyl)urea
The compound was prepared from the compound of Example 74(a) using the
procedures described in Example 78. 1H NMR (300 MHz, CD3OD): δ 8.7 (s, 1H), 8.6
(s, 1H), 8.2 (s, 1H), 8.0 (s, 1H), 7.95 (s, 1H), 7.6-7.7 (m, 5H), 7.5 (s, 1H), 6.9 (d, 1H),
6.3 (s, 2H), 4.0 (s, 3H), 2.4 (s, 3H), 1.4-1.9 (m, 8H). LC-MS (ESI): Calculated mass:
480.56; Observed mass: 481.2 [M+H]+ (RT: 1.517 min).
Example 80.
iY-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methyl-
furan-2-yl)phenyl)morpholine-4-carboxamide
The compound was prepared from the compound of Example 74(a) using the
procedures described in Example 78. 1H NMR (300 MHz, CD3OD): δ 8.5 (s, 1H), 8.0
(s, 1H), 7.95 (s, 1H), 7.9 (s, 1H), 7.8 (s, 2H), 7.6-7.7 (m, 3H), 7.5 (s, 1H), 6.8 (d, 1H),
6.2 (s, 1H), 4.0 (s, 3H), 2.4 (s, 3H), 3.6 (t, 4H), 3.8 (t, 4H). LC-MS (ESI): Calculated
mass: 482.53; Observed mass: 483.1 [M+H]+ (RT: 0.814 min).
Example 81.
N-(3-(5-(l-(2-hydroxyethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-
methylfuran-2-yl)phenyl)acetamide
The compound was prepared from the compound of Example 73(e) using the
procedures described in Example 73. 1H NMR (300 MHz, DMSO-d6): δ 10.1 (s, 1H),
8.6 (s, 1H), 8.4 (s, 1H), 7.7-8.0 (m, 4H), 7.6 (m, 3H), 7.0 (d, 1H), 6.8 (d, 1H), 6.2 (d,
1H), 4.2 (t, 2H), 3.8 (t, 2H), 2.4 (s, 3H), 2.2 (s, 3H). LC-MS (ESI): Calculated mass:
441.48; Observed mass: 442.1[M+H]+ (RT: 0.436 min).

Example 82.
A^-(3-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-5-(5-methylfuran-2-yl)phenyl)acetamide
The compound was prepared from the compound of Example 73(e) using the
procedures described in Example 73. 1HNMR (300 MHz, CD3OD): δ ; 9.5 (s, 1H), 8.3
(s, 1H), 8.1 (m, 3H), 7.95 (m, 4H), 7.7 (m, 1H), 6.8 (d, 1H), 6.2 (s, 1H), 4.20 (m, 2H),
3.7 (m, 2H), 3.0 (s, 6H), 2.4 (s, 3H), 2.2 (s, 3H). LC-MS (ESI): Calculated mass:
468.55; Observed mass: 469.5 [M+H]+ (RT: 0.179 min).
Example 83.
N-(3-(5-methylfuran-2-yl)-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-
benzo[d]imidazol-1 -yl)phenyl)acetamide
The compound was prepared from the compound of Example 73(e) using the
procedures described in Example 73. 1HNMR (300 MHz, CD3OD): δ ; 9.5 (s, 1H), 8.3
(s, 1H), 8.1 (m, 3H), 7.95 (m, 3H), 7.7 (m, 1H), 6.8 (d, 1H), 6.2 (d, 1H), 4.70 (t, 2H),
4.0 (m, 3H), 3.7 (t, 2H), 3.50 (m, 3H), 2.4 (s, 4H), 2.2 (s, 4H). LC-MS (ESI):
Calculated mass: δ10; Observed mass: δ11.2[M+Hf (RT: 0.277min).
Example 84.
N-(3 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(5-methylfuran-2-yl)-
phenyl)acetamide
To a solution of AT-[3-(5-Bromo-benzoimidazol-l-yl)-5-(5-methyl-furan-2-yl)-
phenyl]acetamide of Example 73(e) (0.1 g, 0.243 mmol) in DMF (5 ml) were added
pyrazole (0.022 g, 0.0317 mmol, 1.3 eq.), copper(I) oxide (O.Olg, 0.1 eq.) and cesium
carbonate (0.158g, 0.0487 mmol, 2.0 eq.) and the mixture was heated at 110 °C for a
period of 48 h. The reaction mixture was quenched by addition of water and extracted
with ethyl acetate (3 * 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent wras distilled off under reduced

pressure and the residue was purified by preparative HPLC to give the title product in 68
% yield (0.02 g). 1H NMR (300 MHz, DMSO-4): S ; 9.3 (s, 1H), 8.4 (s, 1H), 8.3 (s,
1H), 7.8-8.1 (m, 4H), 7.6-7.7 (m, 3H), 6.80 (d, 1H), 6.6 (t, 1H), 6.2 (d, 1H), 2.4 (s, 3H),
2.2 (s, 3H), LC-MS (ESI): Calculated mass: 397.43; Observed mass: 398.3 [M+H]+
(RT: 1.382 min).
Example 85.
N-(3 -(5-( 1 H-imidazol-1 -yl)-1 H-benzo [d] imidazol-1 -yl)-5-(5 -methylruran-2-yl)-
phenyl)acetamide
The compound was prepared from the compound of Example 73(e) using the
procedures described in Example 84. *H NMR (300 MHz, DMSO-d6): δ 9.5 (s, 1H), 9.0
(m, 1H), 8.2 (m, 2H), 8.0 (s, 2H), 7.8 (m, 4H), 7.6 (s, 1H), 6.80 (d, 1H), 6.2 (d, 1H), 2.4
(s, 3H), 2.2 (s, 3H), LC-MS (ESI): Calculated mass: 397.43; Observed mass: 398.3
[M+H]+(RT: 0.179 min).
Example 86.
N-(3-(5-(4H-l,2,4-triazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(5-methylfuran-2-
yl)phenyl)acetamide
The compound was prepared from the compound of Example 73(e) using the
procedures described in Example 84. 1H NMR (300 MHz, DMSO-d6): δ ; 10.4 (s, 1H),
9.3 (s, 1H), 8.8 (s, 1H), 8.4 (d, 211), 7.8-8.1 (m, 4H), 7.6 (s, 1H), 6.80 (d, 1H), 6.2 (d,
1H), 2.4 (s, 3H), 2.2 (s, 3H), LC-MS (ESI): Calculated mass: 398.42; Observed mass:
399.2 [M+H]+ (RT: 0.914 min).
Example 87.
N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d] imidazol-1 -yl)-5-( 1 H-pyrrol-1 -
yl)phenyl)acetamide
a) l-(3, 5-Dinitro-phenyl)-lH-pyrrole

A solution of 3,5-dinitroaniline (10 g, 54.644 mmol) and 2,5-dimethoxytetra-
hydrofuran (18.05 g, 136.61 mmol, 2.5 eq.) in acetic acid (122 ml) was heated to 100 °C
for 16 h. Completion of reaction was monitored by TLC. Then the mixture was brought
to room temperature and poured into ice-cold water. The precipitate was filtered,
washed with water (150 ml) and dried to give the product in 54 % yield (8.2 g). LC-MS
(ESI): Calculated mass: 233.18; Observed mass: 233.04 [M+H]+ (RT: 1.667 min).
b) 3-Nitro-5-pyrrol-l-yl-phenylamine
To a solution of l-(3, 5-dinitro-phenyl)-lH-pyrrole (8.2 g, 35.19 mmol) and
pyridine (10 ml) in ethanol (100 ml), at 80 °C, was added a 20 % aqueous solution of
ammonium sulfide (38.4 ml, 140.76 mmol, 4.0 eq.) in water (10 ml). The mixture was
stirred at the same temperature for 4 h. The the reaction mixture was quenched with ice
water (200 ml) and the precipitated solid was filtered. The filtered solid was dried under
vacuum to afford the title product in 98 % yield (7.0 g).
c)N-(3-Nitro-5-pyrrol-l-yl-phenyl)-acetamide
Acetic anhydride (7.0 ml) was added to 3-nitro-5-pyrrol- 1-yl-phenylamine (7.0 g,
34.48 mmol). The mixture was stirred for 30 min at room temperature and subsequently
quenched by the addition of crushed ice. The precipitate formed was filtered and was
washed with cold water to obtain off-white solid. The solid was dried under high
vacuum to give the product in 89 % yield (7.52 g). LC-MS (ESI): Calculated mass:
245.23; Observed mass: 244.1 [M-H]+ (RT: 0.24 min).
d) N-(3 -Amino-5 -pyrrol-1 -yl-phenyl)-acetamide
To a solution of N-(3-nitro-5-pyrrol-l-yl-phenyl)acetamide (7.51 g, 30.61 mmol)
in ethanol (100 ml), were added iron powder (4.273 g, 76.53 mmol, 2.5 eq.) and a
solution of calcium chloride (8.49 g, 76.53 mmol, 2.5 eq.) in water (100 ml). The
reaction mixture was stirred at 80 °C for 2 h and then filtered through a pad of celite.
The celite pad was washed with ethyl acetate (200 ml) and the combined organic layer

was washed with water (100 ml) and brine (25 ml). The solvent was evaporated under
reduced pressure and the residue was purified by column chromatography (20 % ethyl
acetate in hexanes) to give the title compound in 87 % yield (5.7 g). lR NMR (300
MHz, DMSO-d6): δ 9.9 (s, 1H), 8.25 (s, 1H), 7.8 (d, 1H), 7.6 (s, 1H), 7.05 (d, 1H), 6.8
(s, 1H), 6.5 (m, 1H), 6.3 (m, 1H), 5.15 (s, 2H), 2.02 (s, 3H).
e) N-(3-(4-bromo-2-nitrophenylamino)-5-(lH-pyrrol-l-yl) phenyl) acetamide
To a solution of N-(3-amino-5-pyrrol-l-yl-phenyl)acetamide (5 g, 23.23 mmol)
in anhydrous DMF (5 ml), 4-bromo-l-fluoro-2-nitrobenzene (5.11 g, 23.23 mmol) and
potassium fluoride (1.35 g, 23.23 mmol) were added. The mixture was stirred at 110 °C
for overnight. Then the mixture was brought to room temperature and DMF was
removed under vacuum. Residue was subjected to flash column chromategraphy (50 %
ethyl acetate in hexanes) to get the title compound in 63 % yield (6.1 g).
f) N-(3-(2-amino-4-bromophenylamino)-5-(lH-pyrrol-l-yl) phenyl) acetamide
To a solution of N-(3-((4-bromo-2-nitrophenyl)amino)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide (6.0 g, 14.45 mmol) in ethanol (50 ml), iron powder (2.02 g, 36.12
mmol, 2.5 eq.) and calcium chloride (4.01 g, 36.12 mmol, 2.5 eq.) with 50 ml water
were added. The mixture was stirred at 80 °C for 2 h and then filtered through a pad of
celite. The celite pad was washed with ethyl acetate (100 ml) and the combined organic
layer was washed with water (50 ml) and brine (25 ml). The solvent was evaporated
under reduced pressure and the residue was purified by column chromatography (20 %
ethyl acetate in hexanes) to give the title compound in 86 % yield (4.8 g). LC-MS (ESI):
Calculated mass: 385.26; Observed mass: 385 [M+H]+ (RT: 1.659 min).
g) N-(3-(5-bromo-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl) phenyl)
acetamide
Formic acid (12 ml) was added to N-(3-(2-amino-4-bromophenylamino)-5-(lH-
pyrrol-1-yl) phenyl) acetamide (4 g, 10.38 mmol) at room temperature and the mixture

was heated at 100 °C for 2 h. The formic acid was removed under reduced pressure and
the residue was purified over flash column chromatography (3 % methanol in chloro-
form) to afford the product in 76 % yield (3.1 g). LC-MS (ESI): Calculated mass:
395.25; Observed mass: 396.8 [M+H]+ (RT: 1.55 min).
h) N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5 -(1 H-pyrrol-
1 -yl) phenyl) acetamide
To a solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)
phenyl) acetamide (2.0 g, 5.06 mmol) in 1,2-methoxyethane (50 ml), l-methyl-4-
(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (1.58 g, 7.59 mmol, 1.5 eq.),
sodium carbonate (1.34 g, 12.65 mmol, 2.5 eq.) and water (5.0 ml) were added and the
mixture was degassed for 15 min (N2 bubbling). Pd(PPli3)4 (2.92 g, 2.53 mmol, 0.5 eq.)
was added and the mixture was heated at 100 °C for 2 h. The reaction mixture was
quenched by the addition of wrater (100 ml) and the organic phase was separated. The
aqueous phase was extracted with ethyl acetate (2 x 75 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure and the residue was purified column chromatography afford
the title compound in 60 % yield (1.2 g). ]H- NMR (300 MHz, CD3OD): δ 8.53 (s, 1H),
8.0 (s, 1H), 7.9 (s, HI), 7.82 (m, 2H), 7.79 (m, HI), 7.7 (d, 1H), 7.6 (m, 1H), 7.48 (m,
1H), 7.29 (m, 2H), 6.31 (m, 2H), 3.95 (s, 3H), 2.15 (s, 3H); LC-MS (ESI): Calculated
mass: 396.44; Observed mass: 396.8 [M+H]+ (RT: 0.63 min).
Example 88.
N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrrol-1 -
y l)pheny l)methanes ulfonamide
a) 3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-(1 H-pyrrol-1 -
yl)aniline
A mixture of 20 % sodium hydroxide (5 ml) and N-(3-(5-(1-methyl-lH-pyrazol-
4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl) phenyl)acetamide of Example 87

(1.15 g, 2.9 mmol) in 25 ml ethanol was heated at 100 °C for 2 h. The mixture was
diluted with ethyl acetate (100 ml) and the organic layer was washed with water (50 ml)
and brine (25 ml). The solvent was removed under reduced pressure and the crude was
purified by column chromatography over silica gel to give the product in 68 % yield (0.7
g)-
b) N-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-(l H-pyrrol-
1-yl) phenyl)methanesulfonamide
To a solution of 3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(lH-pyrrol-l-yl)aniline (70 mg, 0.198 mmol) in DCM (1 ml) were added pyridine (0.5
ml) and methanesulfonyl chloride (27 mg, 0.237 mmol, 1.2 eq.) and the mixture was
stirred at room temperature for 12 h. Pyridine was removed under reduced pressure and
the crude was purified by preparative HPLC to give the title product in 12 % yield (10
mg). JH- NMR (300 MHz, DMSO-d6): δ: 10.2 (s, 1H), 8.7 (s, 1H), 8.21 (s, 1H), 7.99
(d, 2H), 7.7-7.61 (m, 3H), 7.45 (t, 2H), 7.38 (d, 2H), 6.33 (t, 2H), 3.88 (s, 3H), 3.2 (s,
3H); LC-MS (ESI): Calculated mass: 432.5; Observed mass: 433.1 [M+H]+ (RT: 0.88
min).
Example 89.
N-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-l -yl)-5-( 1 H-pyrrol-1 -
yl)phenyl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 87 using the
procedures described in Example 88. 1H- NMR (300 MHz, DMSCW6): δ 10.2 (s, 1H),
8.71 (s, 1H), 8.2 (s, 1H), 7.99 (m, 1H), 7.95 (s, 1H), 7.68-7.59 (m, 3H), 7.44-7.41 (m,
4H), 6.31 (m, 2H), 3.95 (s, 3H), 2.95 (m, 1H), 1.0 (m, 4H); LC-MS (ESI): Calculated
mass: 458.54; Observed mass: 459.2 [M+H]+ (RT: 1.29 min).
Example 90.
N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5 -(1 H-pyrrol-1 -
yl)phenyl)benzenesulfonamide

The compound was prepared from the compound of Example 87 using the
procedures described in Example 88. 1H-NMR (300 MHz, CD3OD): 6 8.35 (s, 1H),
7.93 (s, 1H), 7.83-7.78 (m, 4H), 7.58-7.55 (m, 1H), 7.51-7.47 (m, 3H), 7.36 (t, 1H),
7.32 (d, 1H), 7.21 t, 1H), 7.14 (t, 1H), 7.12-7.11 (m, 2H), 6.22 (t, 2H), 3.9 (s, 3H); LC-
MS (ESI): Calculated mass: 494.57; Observed mass: 495 [M+H]+ (RT: 1.71 min).
Example 91.
l-(furan-2-ylmethyl)-3-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-
l-yl)-5-(l H-pyrrol-1 -yl)phenyl)urea
To a solution of 3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(lH-pyrrol-l-yl)aniline of Example 88(a) (70 mg, 0.198 mmol) in DCM (1 ml) at 0 °C
were added TEA (triethylamine) (0.055 ml, 0.396 mmol, 2.0 eq.) and 2-(isocyanato-
methyl)furan (29 mg, 0.237 mmol, 1.2 eq.). The mixture was stirred at room
temperature for 16 h. The solvent was removed under reduced pressure and the residue
was purified by preparative HPLC to afford the title compound in 40 % yield (38 mg).
1H- NMR (300 MHz, CD3OD): δ 9.0 (s, 1H), 8.07 (s, 1H), 7.97 (s, 1H), 7.92 (s, 1H),
7.81-7.74 (m, 3H), 7.63 (s, 1H), 7.44 (m, 2H), 7.3 (m, 2H), 6.36-6.31 (m, 4H), 4.41 (s,
2H), 3.96 (s, 3H); LC-MS (ESI): Calculated mass: 477.52; Observed mass: 478.1
LM+H]+(RT: 1.393 min).
Example 92.
1 -cyclopentyl-3 -(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5 -
(1 H-pyrrol-1 -yl)phenyl)urea
The compound was prepared from the compound of Example 87 using the
procedures described in Example 91. 1H- NMR (300 MHz, CD3OD): δ 9.52 (s, 1H),
8.16 (s, 1H), 8.03 (s, 1H), 7.98 (s, 1H), 7.88-7.84 (m, 3H), 7.65 (s, 1H), 7.47 (s, 1H),
7.3 (m, 2H), 6.35 (m, 2H), 4.1 (m, 1H), 3.95 (s, 3H), 2.05 (m, 2H), 1.8-1.6 (m, 4H),
1.51-1.48 (m, 2H); LC-MS (ESI): Calculated mass: 465.55; Observed mass: 466.1
[M+H]+(RT: 1.45 min).

Example 93.
N-(3-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-5-(lH-pyrrol-l-yl)phenyl)acetamide
The compound was prepared from the compound of Example 87(g) using the
procedures described in Example 87. 1H- NMR (300 MHz, CD3OD): δ 8.42 (s, 1H), 8.0
(s, 1H), 7.82-7.8 (m, 2H), 7.75 (s, 1H), 7.65 (s, 1H), 7.6 (d, 1H), 7.51 (d, 1H), 7.38 (s,
1H), 7.19 (m, 2H), 6.21 (m, 2H), 4.32 (t, 2H), 3.0 (t, 2H), 2.4 (s, 6H), 2.08 (s, 3H); LC-
MS (ESI): Calculated mass: 453.23; Observed mass: 453.9 [M+H]+ (RT: 0.112 min).
Example 94.
N-(3-(5-(l -(2-(dimethylamino)ethyl)-1 H-pyrazol-4-yl)-l H-benzo[d]imidazol-l -
yl)-5 -(1 H-pyrrol-1 -yl)phenyl)benzenesulfonamide
The compound was prepared from the compound of Example 93 using the
procedures described in Example 88. 1H- NMR (300 MHz, DMSO-d6): δ 10.91 (s, 1H),
8.66 (s, 1H), 8.36 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.91-7.89 (m, 2H), 7.7-7.59 (m,
5H), 7.36-7.29 (m, 4H), 7.22 (m, 1H), 6.32 (t, 2H), 4.57 (t, 2H), 3.64 (m, 2H), 2.86 (d,
6H); LC-MS (ESI): Calculated mass: δ51.66; Observed mass: δ52.2 [M+H]+ (RT: 0.54
min).
Example 95.
N-(3-(5-(6-methoxypyridin-3-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide
The compound was prepared using the procedures described in Example 87. lH-
NMR (300 MHz, CD3OD): δ 9.0 (s, 1H), 8.37 (d, 1H), 7.96 (dd, 1H), 7.92 (s, 1H),
7.89-7.87 (m, 1H), 7.78 (d, 1H), 7.71 (t, 2H), 7.68-7.65 (m, 1H), 7.49 (t, 1H), 7.2 (t,
2H), 6.85 (d, 1H), 6.25 (t, 2H), 3.89 (s, 3H), 2.1 (s, 3H); LC-MS (ESI): Calculated mass:
423.47; Observed mass: 424.1[M+H]+ (RT: 1.518 min).

Example 96.
N-(3 -(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-5 -(1 H-pyrrol-1 -yl)-
phenyl)acetamide
To a solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)
phenyl) acetamide of Example 87(g) (2.0 g, 5.06 mmol) in DMF (50 ml) were added
pyrazole (0.69 g, 10.12 mmol, 2.0 eq.), copper(I) oxide (0.145 g, 1.01 mmol, 0.2 eq.)
and cesium carbonate (3.3 g, 10.12 mmol, 2.0 eq.) and the mixture was heated at 110 °C
for 16 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography to give the title product in 78 % yield (1.5 g).
1H- NMR (300 MHz, DMSO-d6): δ 10.2 (s, 1H), 8.79 (s, 1H), 8.61 (d, 1H), 8.24 (d,
1H), 7.94-7.91 (m, 1H), 7.87-7.81 (m, 3H), 7.76 (d, 1H), 7.64-7.63 (m, 1H), 7.43-7.42
(m, 2H), 6.57 (t, 1H), 6.33 (m, 2H), 2.13 (s, 3H); LC-MS (ESI): Calculated mass:
382.42; Observed mass: 383.1 [M+H]+ (RT: 1.376 min).
Example 97.
N-(3-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)-
phenyl)ethanesulfonamide
a) 3-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-1 -yl)aniline
A mixture of 10 % NaOH (5 ml) and N-(3-(5-(lH-pyrazol-l-yl)-lH-benzo[d]-
imidazol-l-yl)-5-(l H-pyrrol- l-yl)phenyl)acetamide of Example 96 (1.45 g, 3.79 mmol)
in 25 ml ethanol was heated at 100 °C for 2 h. The mixture was diluted with ethyl
acetate (100 ml) and the organic layer was washed with wrater (50 ml) and brine (25 ml).
The solvent was removed under reduced pressure and the residue was purified by
column chromatography over silica gel to give the product in 85 % yield (1.1 g).
b) N-(3-(5 -(1 H-pyrazol-1 -yl)-1 H-benzo[d] imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl)-
phenyl)ethanesulfonamide

To a solution of 3-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-
pyrrol-l-yl)aniline (70 mg, 0.206 mmol) in DCM (2 ml) were added pyridine (0.033 ml,
0.411 mmol, 2.0 eq.) and ethanesulfonyl chloride (32 mg, 0.247 mmol, 1.2 eq.) and the
mixture was stirred at room temperature for 12 h. Pyridine was removed under reduced
pressure and the residue was purified by preparative HPLC to afford the title product in
63 % yield (56 mg). 1H- NMR (300 MHz, DMSO-d6): δ 10.35 (s, 1H), 8.83 (s, 1H),
8.62 (d, 1H), 8.26 (d, 1H), 7.95 (dd, 1H), 7.82-7.78 (m, 2H), 7.69 (s, 1H), 7.46-7.42 (m,
4H), 6.58 (t, 1H), 6.35 (t, 2H), 3.34-3.32 (m, 2H), 1.28 (t, 3H); LC-MS (ESI):
Calculated mass: 432.5; Observed mass: 433.2 [M+H]+ (RT: 1.43 min).
Example 98.
N-(3 -(5-( 1 H-pyrazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl)-
phenyl)propane-2-sulfonamide
The compound was prepared from the compound of Example 96 using the
procedures described in Example 87. 1H- NMR (300 MHz, DMSO-d6): δ 10.3 (s, 1H),
8.81 (s, 1H), 8.6 (d, IH), 8.25 (d, 1H), 7.95-7.92 (m, 1H), 7.79-7.76 (m, 2H), 7.66 (m,
1H), 7.43 (m, 4H), 6.57-6.56 (m, IH), 6.34-6.33 (m, 2H), 3.53-3.5 (m, IH), 1.31 (d,
6H); LC-MS (ESI): Calculated mass: 446.52: Observed mass: 447.2 [M+H]+ (RT: 1.5
min).
Example 99.
N-(3 -(5-( 1 -methyl-1H-1,2,3-triazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-(l H-
pyrrol-1 -yl)phenyl)acetamide
a)N-(3-(4-iodo-2-nitrophenylamino)-5-(lH-pyrrol-l-yl)phenyl)acetamide
A solution of N-(3-amino-5-pyrrol-l-yl-phenyl)acetamide of Example 87(d) (5.0
g, 18.72 mmol), 1-fluoro-4-iodo-2-nitrobenzene (4.02 g, 18.72 mmol, 1.0 eq.) and
potassium fluoride (1.08 g, 18.72 mmol, 1.0 eq.) in DMF (30 ml) was heated at 130 °C
for 5 h. The reaction mixture was quenched with water and extracted with ethyl acetate

(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (60-120 silica gel, 50 % ethyl acetate in
hexane) to give the title product in 49 % yield (4.3 g).
b) N-(3-((2-amino-4-iodophenyl)amino)-5-( 1 H-pyrrol-1 -yl)phenyl)acetamide
To a solution of N-(3-(4-iodo-2-nitrophenylamino)-5-(l H-pyrrol-1-yl)phenyl)-
acetamide (0.5 g, 1.08 mmol) in THF (30 ml) were added a solution of ammonium
chloride (0.289 g, 5.41 mmol, 5 eq.) in water (5 ml) and zinc (0.354 g, 5.41 mmol, 5
eq.). The mixture was stirred at room temperature for 0.5 h and filtered. The filtrate was
diluted with water and extracted with ethyl acetate (3 x 100 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 75 % yield (0.35 g). *H
NMR(300 MHz, DMSO-d6): δ 9.88 (s, 1H), 7.38 (s, 1H), 7.19 (s, 1H), 7.09-7.06 (m,
3H), 6.84-6.8 (m, 3H), 6.51 (m, 1H), 6.22 (t, 2H), 5.04 (br s, 2H), 2.0 (s, 3H).
c) N-(3 -(5 -iodo-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrrol-1 -yl) phenyl)
acetamide
A mixture of N-(3-((2-amino-4-iodophenyl)amino)-5-(1 H-pyrrol-1 -yl)phenyl)-
acetamide (0.35 g, 0.81 mmol) and formic acid (10 ml) was heated at 100 °C for 30 min.
The formic acid was distilled off under reduced pressure and the residue was dissolved
in ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 84 % yield (0.3 g). 1H NMR, 300 MHz: (DMSO-d6): δ 10.4 (s, 1H), 8.7 (s,
1H), 8.18 (s, 1H), 7.82 (s, 2H), 7.67-7.54 (m, 3H), 7.4 (s, 2H), 6.32 (m, 2H), 2.05 (s,
3H).
d) N-(3-(lH-pyrrol-l-yl)-5-(5-((trimethylsilyl) ethynyl)-lH-benzo[d]imidazol-l-
yl) phenyl) acetamide

A solution of N-(3-(5-iodo-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl)
phenyl)acetamide (3.0 g, 7.4 mmol) in DMF-Et3N (1:1; 60 ml) was degassed by N2
bubbling for 15 min. Pd(PPh3)4 (1.2g, 11.9 mmol, 0.1 eq.), copper® iodide (0.2 g, 11.9
mmol, 0.1 eq.) and ethynyltrimethylsilane (2.2 ml, 49.2 mmol, 2 eq.) were added
sequentially and the mixture was stirred for 12 h at room temperature. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 * 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 60 % ethyl acetate in hexane) to give the
title product in 71 % yield (2.0 g). LHNMR, 300 MHz: (DMSO-d6): δ 10.4 (s, 1H), 8.85
(s, 1H), 7.9-7.8 (m, 2H), 7.75-7.5 (m, 6H), 7.45 (t, 2H), 2.05 (s, 3H), 0.2 (s, 9H); LC-
MS (ESI): Calculated mass: 412.56; Observed mass: 413 [M+H]+ (RT: 1.55 min).
e)N-(3-(5-ethynyl-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)acet-
amide
To a solution of N-(3-(lH-pyrrol-l-yl)-5-(5-((trimethylsilyl) ethynyl)-lH-
benzo[d]imidazol-l-yl) phenyl) acetamide (2.0g, 4.85 mmol) in THF at 0 °C was added
TBAF (1M in THF; 2.0 ml, 9.7 mmol, 2 eq.) and the mixture was stirred for 0.5 h. The
mixture was filtered over a pad of silica and distilled to give the product in 96 % yield
(1.6 g). LC-MS (ESI): Calculated mass: 340.38; Observed mass: 341.1 [M+H]+ (RT:
1.518 min).
f) N-(3 -(5 -(1 -methyl-1H-1,2,3-triazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5 -(1H-
pyrrol-1 -yl)phenyl)acetamide
A mixture of N-(3-(5-ethynyl-lH-benzo[dJimidazol-l-yl)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide (l.Og, 29.4 mmol), sodium azide (0.19 g, 29.4 mmol, 1.0 eq.), methyl
iodide (0.4 g, 29.4 mmol, 1.0 eq.), sodium ascorbate (0.6g, 29.4 mmol, 1.0 eq.) and
copper sulfate pentahydrate (0.36 g, 14.7 mmol, 0.5 eq.) in DMSO, DCM and water
(1:1:1, 15:12:12 ml) was stirred for 12 h at room temperature. The reaction mixture was
quenched with water and the precipitate formed was filtered and dried to give the crude

product which was purified by preparative HPLC to give the title product in 15 % yield
(0.02 g). LC-MS (ESI): Calculated mass: 397.43; Observed mass: 398.1 [M+H]+ (RT:
0.453 min).
Example 100.
N-(3 -(5 -(1 -methyl-1H-1,2,3 -triazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1H-
pyrrol-1 -yl)phenyl)methanesulfonamide
a) 3-(5-(l -methyl-1H-1,2,3-triazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1H-
pyrrol-1 -yl)aniline
A mixture of 20 % sodium hydroxide (5 ml) and N-(3-(5-(l-methyl-lH-l,2,3-
triazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-(1 H-pyrrol-1 -yl)phenyl)acetamide of
Example 99 (1.0 g, 2.52 mmol) in 10 ml ethanol was heated at 100 °C for 3 h. The
mixture was diluted with ethyl acetate (100 ml) and the organic layer was washed with
water (50 ml) and brine (25 ml). The solvent was removed under reduced pressure and
the residue was purified by column chromatography over silica gel to afford the product
in 73 % yield (0.65 g). LC-MS (ESI): Calculated mass: 355.4; Observed mass: 356.3
[M+H]+ (RT: 0.49 min).
b)N-(3-(5-(l-methyl-lH-l,2,3-triazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-
pyrrol-1 -yl)phenyl)methanesulfonamide
To a solution of 3-(5-(l-methyl-lH-l,2,3-triazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-5-(lH-pyrrol-l-yl)aniline (100 mg, 0.281 mmol) in DCM (5 ml) were added pyridine
(45 mg, 0.563 mmol, 2.0 eq.) and methanesulfonyl chloride (26 mg, 0.225 mmol, 0.8
eq.) and the mixture was stirred at room temperature for 12 h. Pyridine was removed
under reduced pressure and the residue was purified by preparative HPLC to afford the
title product in 7 % yield (8 mg). 1H NMR, 300 MHz: (DMSO-d6): δ 10.33 (s, 1H), 9.01
(s, 1H), 8.64 (s, 1H), 8.27 (s, 1H), 7.97-7.94 (m, 1H), 7.83 (d, 1H), 7.71 (s, 1H), 7.46-
7.42 (m, 4H), 6.35-6.34 (m, 2H), 4.12 (s, 3H), 3.21 (s, 3H); LC-MS (ESI): Calculated
mass: 433.49; Observed mass: 434.3 [M+H]+ (RT: 0.67 min).

Example 101.
N-(3-(5 -(1 -methyl-1H-1,2,3 -triazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1H-
pyrrol-1 -yl)phenyl)ethanesulfonamide
The compound was prepared from the compound of Example 99 using the
procedures described in Example 100. 1H NMR, 300 MHz: (DMSO-d6): δ 10.37 (s, 1H),
8.97 (s, 1H), 8.63 (s, 1H), 8.26 (s, 1H), 7.95-7.93 (m, 1H), 7.8 (d, 1H), 7.67 (m, 1H),
7.45-7.42 (m, 4H), 6.34 (t, 2H), 4.2 (s, 3H), 2.4 (m, 2H), 1.2 (d, 3H); LC-MS (ESI):
Calculated mass: 447.51; Observed mass: 449.1 [M+H]+ (RT: 0.97 min).
Example 102.
N-(3 -(5 -(1 -methyl-1H-1,2,3-triazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1H-
pyrrol-1 -yl)phenyl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 99 using the
procedures described in Example 100. 1HNMR, 300MHz: (DMSO-d6): δ 10.3 (s, 1H),
8.8 (s, 1H), 8.61 (s, 1H), 8.25 (s, 1H), 7.91 (d, 1H), 7.78 (d, 1H), 7.69 (s, 1H), 7.46-7.43
(m, 4H), 6.34 (t, 2H), 4.12 (s, 3H), 2.94 (m, 1H), 1.04-1.02 (m, 4H); LC-MS (ESI):
Calculated mass: 459.52; Observed mass: 460.1 [M+H]+ (RT: 1.22 min).
Example 103.
N-(3-(5-(l-methyl-lH-l,2,3-triazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-
pyrrol-l-yl)phenyl)benzenesulfonamide
The compound was prepared from the compound of Example 99 using the
procedures described in Example 100. ]H NMR, 300 MHz: (DMSO-d6): δ 10.91 (s, 1H),
8.69 (s, 1H), 8.61 (s, 1H), 8.21 (s, 1H), 7.92-7.89 (m, 3H), 7.67-7.62 (m, 4H), 7.37-7.32
(m, 4H), 7.20 (s, 1H), 6.32 (d, 2H), 4.11 (s, 3H); LC-MS (ESI): Calculated mass:495.56;
Observed mass: 496.1 [M+H]+ (RT: 1.42 min).
Example 104.

l-(furan-2-ylmethyl)-3-(3-(5-(l-methyl-lH-L2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-5 -(1 H-pyrrol-1 -yl)phenyl)urea
To a solution of 3-(5-(l-methyl-lH-l,2,3-triazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-5-(lH-pyrrol-l-yl)aniline of Example 100(a) (100 mg, 0.281 mmol) in DCM (10 ml)
at 0 °C was added 2-(isocyanatomethyl)furan (35 mg, 0.281 mmol, 1.0 eq.) and the
mixture was stirred at room temperature for 16 h. The solvent was removed under
reduced pressure and the residue was purified by preparative HPLC to give the title
compound in 13 % yield (18 mg). 1HNMR, 300 MHz: (DMSO-d6): δ 9.05 (s, 1H), 8.8
(s, 1H), 8.6 (s, 1H), 8.24 (s, 1H), 7.92-7.9 (m, 1H), 7.81 (d, 1H), 7.72-7.60 (m, 4H),
7.48-7.41 (m, 3H), 6.89 (t, 1H), 6.41 (m, 1H), 6.32-6.28 (m, 2H), 4.33 (d, 2H), 4.12 (s,
3H); LC-MS (ESI): Calculated mass:478.51 ; Observed mass: 479.2 [M+Hf (RT: 1.39
min).
Example 105.
N-(3-(5-( 1 -(2-morpholinoethyl)-1H-1,2,3 -triazol-4-yl)-l H-benzo[d] imidazol-1 -
yl)-5-(lH-pyrrol-l-yl)phenyl)acetamide
A mixture of N-(3-(5-ethynyl-lH-benzo[d]imidazol-l -yl)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide of Example 99(e) (100 mg, 0.294 mmol), 4-(2-azidoethyl)morpholine
(55 mg, 0.353 mmol, 1.2 eq.), sodium ascorbate (58 mg, 0.294 mmol, 1.0 eq.) and
copper sulfate pentahydrate (37 mg, 0.147 mmol, 0.5 eq.) in DMSO, DCM and water
(1:1:1,3 ml) was stirred for 12 h at room temperature. The reaction mixture was
quenched with water and the precipitate formed was filtered and dried to give the crude
product which was purified by preparative HPLC to give the title product in 7 % yield
(10 mg). 1HNMR, 300 MHz: (DMSO-d6): δ 10.46 (s, 1H), 8.83 (s, 1H), 8.73 (s, 1H),
8.28 (s, 1H), 7.92 (m, 2H), 7.84-7.81 (m, 2H), 7.63 (s, 1H), 7.43-7.42 (m, 2H), 6.34 (m,
2H), 4.82 (t, 2H), 4.01 (m, 4H), 3.7 (m, 2H), 2.51-2.43 (m, 4H), 2.05 (s, 3H); LC-MS
(ESI): Calculated mass: 496.56; Observed mass: 497 [M+Hf (RT: 0.08 min).
Example 106.

N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)-
acetamide
a)N-(3-(4-formyl-2-nitrophenylamino)-5-(lH-pyrrol-l-yl)phenyl)acetamide
A solution of N-(3-amino-5-(lH-pyrrol-l-yl)phenyl)acetamide of Example 87(d)
(5.5 g, 25.7 mmol), 4-fluoro-3-nitrobenzaldehyde of Intermediate Example 4 (3.86 g,
25.7 mmol, 1.0 eq.) and potassium fluoride (1.49 g, 25.7 mmol, 1.0 eq.) in DMF (5 ml)
was heated at 130 °C for 4 h. The mixture was quenched with water and extracted with
ethyl acetate (3 x 100 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure
and the residue was purified by column chromatography (60-120 silica gel, 40% ethyl
acetate in hexane) to give the title product in 38 % yield (3.58 g). 1H NMR (300 MHz,
DMSO-d6): 6 10.05 (s, 1H), 9.86 (s, 1H), 8.71 (s, 1H), 7.95 (d, 1H), 7.67 (m, 2H), 7.50
(s, 1H), 7.32-7.29 (m, 5H), 6.29 (s, 1H), 2.08 (s, 3H).
b)N-(3-(2-nitro-4-(oxazol-5-yl)phenylamino)-5-(lH-pyrrol-l-yl)phenyl)acet-
amide
To a solution of N-(3-(4-formyl-2-nitrophenylamino)-5-(lH-pyrrol-l-yl)phenyl)-
acetamide (2.5 g, 6.88 mmol) in methanol (15 ml) was added potassium carbonate (1.04
g, 7.57 mmol, 1,1 eq.) and the mixture was stirred for 10 min at room temperature.
Toluenesulfonylmethyl isocyanide (1.48 g, 7.57 mmol, 1.1 eq.) was added and the
mixture was refluxed for 4 h. The solvent was distilled off and water was added to the
crude. The mixture was extracted with ethyl acetate (3 x 100 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 70% ethyl acetate in hexane) to give the title product
in 57% yield (1.58 g). [HNMR(300 MHz, DMSO-d6): δ 10.05 (d, 1H), 10.32 (d, 1H),
9.87 (s, 1H), 7.81 (s, 1H), 7.98-7.92 (m, 1H), 7.85-7.60 (m, 3H), 7.55 (s, 1H), 7.32-7.29
(m, 4H), 7.29 (s, 1H), 2.08 (s, 3H).

c) N-(3-(2-amino-4-(oxazol-5-yl)phenylamino)-5-(lH-pyrrol-l-yl)phenyl)acet-
amide
To a solution of N-(3-(2-nitro-4-(oxazol-5-yl)phenylamino)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide (1.58 g, 3.9 mmol) in methanol (30 ml) and ethylacetate (15 ml) was
added 10 % Pd/C (300 mg, 0.2 eq.) and the reaction vessel was purged with nitrogen gas
for 5 min. The mixture was then hydrogenated with H2 balloon for 12 h. The mixture
was filtered through a pad of celite and the filtrate was concentrated under reduced
pressure to afford the title compound in 68 % yield (1.0 g).
d)N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)-
acetamide
A mixture ofN-(3-(2-amino-4-(oxazol-5-yl)phenylamino)-5-(lH-pyrrol-l-yl)-
phenyl)acetamide (0.4 g, 1.07 mmol) and formic acid (4 ml) was heated at 100 °C for 30
min. The formic acid was distilled off under reduced pressure and the residue was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by preparative HPLC to give the title product in 12 % yield (50
mg). 1H NMR (300 MHz, DMSO-d6): δ 10.43 (s, 1H), 8.84 (s, 1H), 8.47 (s, 1H), 8.17
(s, 1H), 7.87-7.77 (m, 5H), 7.63 (s, 1H), 7.42 (t, 2H), 6.34 (t, 2H), 2.13 (s, 3H); LC-MS
(ESI): Calculated mass: 383.40; Observed mass: 384.1 [M+H]+ (RT: 1.108 min).
Example 107.
N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)-
propane-2-sulfonamide
a) 3-(5-(oxazol-5-yl)-1 H-benzo[d]imidazol-1 -yl)-5-(1 H-pyrrol-1 -yl)aniline
To a solution of N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-
l-yl)phenyl)acetamide of Example 106 (800 mg, 2.1 mmol) in ethanol (15 ml) was
added aqueous solution of NaOH (0.72 g, 18.06 mmol, 8.6 eq.) and the mixture was

heated at 85 °C for 5 h. The reaction mixture was quenched with water and extracted
with ethylacetate (3 x 50 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 70 % yield (0.5 g).
b) N-(3-(5-(oxazol-5-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrrol-1 -yl)phenyl)-
propane-2-sulfonamide
To a solution of 3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-
yl)aniline (80 mg, 0.23 mmol) in DCM (2 ml) was added pyridine (37 mg, 0.47 mmol,
2.0 eq.) followed by propane-2-sulfonyl chloride (39 mg, 0.28 mmol, 1.2 eq.). The
mixture was stirred for 1 h, quenched with water and extracted with DCM (3x50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 14 % yield (14 mg). 1H NMR
(300 MHz, DMSO-d6): δ 10.29 (s, 1H), 8.80 (s, 1H), 8.46 (s, 1H), 8.17 (s, 1H), 7.82-
7.86 (m, 3H), 7.68 (s, 1H), 7.46-7.40 (m, 4H), 6.34 (t, 2H), 3.30 (m, 1H), 2.51-2.50 (m,
6H); LC-MS (ESI): Calculated mass: 447.51; Observed mass: 448.1 [M+H]+ (RT: 2.001
min).
Example 108.
N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)-
cyclopropanesulfonamide
The compound was prepared from the compound of Example 106 using the
procedures described in Example 107. 1H NMR (300 MHz, DMSO-d6): δ 10.35 (s, 1H),
8.87 (s, 1H), 8.52 (s, 1H), 8.22 (s, 1H), 7.82 (d, 3H), 7.74-7.35 (m, 1H), 7.5-7.45 (m,
4H), 6.39 (t, 2H), 3.04-2.95 (m, 1H), 1.08-1.07 (m, 4H); LC-MS (ESI): Calculated
mass: 445.49; Observed mass: 446.1 [M+H]+ (RT: 1.43 min).
Example 109.

N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-
yl)phenyl)ethanesulfonamide
The compound was prepared from the compound of Example 87 using the
procedures described in Example 88. 1H NMR (300 MHz, DMSO-d6): δ 10.3 (s, 1H),
8.67 (s, 1H), 8.2 (s, 1H), 8.0 (s, 1H), 7.95 (s, 1H), 7.67-7.61 (m, 3H), 7.43-7.39 (m, 4H),
6.38 (s, 2H), 3.88 (s, 3H), 3.32 (quartet, 2H), 1.27 (t, 3H); LC-MS (ESI): Calculated
mass: 446.52; Observed mass: 447.1 [M+H]+ (RT: 1.25 min).
Example 110.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-
yl)phenyl)propane-2-sulfonamide
The compound was prepared from the compound of Example 87 using the
procedures described in Example 88. [H NMR (400 MHz, DMSO-c?6): δ 10.34 (s, 1H),
8.89 (s, 1H), 8.23 (s, 1H), 8.01 (s, 1H), 7.97 (s, 1H), 7.69-7.65 (m, 3H), 7.44-7.41 (m,
4H), 7.64 (d, 2H), 3.89 (s, 3H), 3.51-3.50 (m, 1H), 1.31 (d, 6H); LC-MS (ESI):
Calculated mass: 460.55; Observed mass: 461.1 [M+H]+ (RT: 1.377 min).
Example 111.
N-(3-(5-( 1 -cyclopentyl-1 H-pyrazol-4-yl)-1 H-benzo[d] imidazol-1 -yl)-5 -(1H-
pyrrol-1 -yl)phenyl)acetamide
The compound was prepared using the procedures described in Example 87. 1H
NMR (300 MHz DMSO-d6): δ 10.45 (s, 1H), 8.96 (s, 1H), 8.34 (s, 1H), 8.04 (s, 1H),
7.98 (s, 1H), 7.91 (s, 1H), 7.83 (s, 1H), 7.72-7.68 (m, 2H), 7.64 (s, 1H), 7.42 (t, 2H),
6.34 (t, 2H), 4.68-4.57 (m, 1H), 2.14 (s, 3H), 2.08-1.93 (m, 4H), 1.87-1.73 (m, 2H),
1.72-1.60 (m, 2H); LC-MS (ESI): Calculated mass: 450.53; Observed mass: 451.2
[M+H]+(RT: 1.509 min).
Example 112.

N-(3 -(5-( 1 -(3 -hydroxy-3-methylbutyl)-1H-1,2,3 -triazol-4-yl)-1 H-benzo [d] -
imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl)phenyl)acetamide
A mixture of N-(3-(5-ethynyl-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl>
phenyl)acetamide of Example 99(e) (0.3 g, 0.88 mmol), 4-azido-2-methylbutan-2-ol of
Intermediate Example 6 (0.17 g, 1.06 mmol, 1.2 eq.), sodium-(L)-ascorbate (0.17 g,
0.88 mmol, 1.0 eq.) and copper sulfate pentahydrate (0.11 g, 0.44 mmol, 0.5 eq.) in
DCM (2 ml), DMSO (2 ml) and water (2 ml) was stirred for 12 h at room temperature.
The reaction mixture was quenched with water and the precipitate was filtered and
dried. The crude product was purified by preparative HPLC to give the product in 48 %
yield (0.2 g). 'il NMR (300 MHz, DMSO-d6): δ 10.42 (s, 1H), 8.86 (s, 1H), 8.68 (s,
1H), 8.23 (s, 1H), 7.93-7.77 (m, 4H), 7.62 (s, 1H), 7.40 (t, 2H), 6.31 (t, 2H), 4.70 (t,
2H), 3.40 (br s, 1H), 2.48 (t, 2H), 2.11 (s, 3H), 1.16 (s, 6H); LC-MS (ESI): Calculated
mass: 469.54; Observed mass: 470.2 [M+H]+ (RT: 0.666 min).
Example 113.
N-(3-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-triazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-5-( 1 H-pyrrol-1 -yl)phenyl)ethanesulfonamide
a) 4-(4-( 1 -(3-amino-5-( 1 H-pyrrol-1 -yl)phenyl)-1 H-benzo[d]imidazol-5-yl)-1H-
l,2,3-triazol-l-yl)-2-methylbutan-2-ol
To a solution of N-(3-(5-(l-(3-hydroxy-3-methylbutyl)-lH-l,2,3-triazol-4-yl)-
lH-benzo[d]imidazoI-l-yl)-5-(lH-pyrrol-l-yl)phenyl)acetamide of Example 112 (150
mg, 0.32 mmol) in ethanol (10 ml) was added aqueous solution of NaOH (160 mg, 4
mmol, 12.5 eq.) and the mixture was heated at 80 °C for 2 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 * 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 58 % yield (80 mg).
b) N-(3 -(5-( 1 -(3 -hydroxy-3 -methylbutyl)-1H-1,2,3-triazol-4-yl)-1 H-benzo[d] -
imidazol-1 -yl)-5-(l H-pyrrol-1 -yl)phenyl)ethanesulfonamide

To a solution of 4-(4-(l-(3-amino-5-(lH-pyrrol-l-yl)phenyl)-lH-benzo[d]-
imidazol-5-yl)-lH-l,2,3-triazol-l-yl)-2-methylbutan-2-ol (100 mg, 0.234 mmol) in
DCM (5 ml) was added pyridine (36 mg, 0.47 mmol, 2 eq.) followed by ethanesulfonyl
chloride (23 mg, 0.187 mmol, 0.8 eq.). The mixture was stirred for 2 h, quenched with
water and extracted with DCM (3 x 50 ml). The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 10
% yield (12 mg). *H NMR (300 MHz, DMSO-d6): δ 10.35 (s, 1H), 8.88 (s, 1H), 8.70 (s,
1H), 8.25 (s, 1H), 7.93 (dd, 1H), 7.78 (d, 1H), 7.68 (m, 1H), 7.45-7.41 (m, 4H), 6.34 (t,
2H), 4.52-4.46 (m, 2H) 3.37-3.30 (m, 5H), 1.27 (t, 3H), 1.18 (s, 6H); LC-MS (ESI):
Calculated mass: δ19.62; Observed mass: δ20.2 [M+H]+ (RT: 1.17 min).
Example 114.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-
1 -yl)phenyl)acetamide
a) N-(3-nitro-5 -(1 H-pyrazol-1 -yl)phenyl)acetamide
To a solution of N-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (10 g,
38.6 mmol) in DMF (100 ml) were added pyrazole (5.26 g, 77.2 mmol, 2.0 eq.),
copper(I) oxide (1.104 g, 7.72 mmol, 0.2 eq.) and cesium carbonate (25.15 g, 77.2
mmol, 2.0 eq.) and the mixture was heated at 120 °C for 16 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 300 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography over silica gel (30 % ethyl acetate in hexane) to afford the title
compound in 86 % yield (8.2 g). 1H NMR (300 MHz, DMSO-cfc): § 10.62 (s, 1H), 8.7
(d, 1H), 8.5-8.48 (m, 2H), 8.32 (t, 1H), 7.84 (d, 1H), 6.62 (t, 1H), 2.08 (s, 3H); LC-MS
(ESI): Calculated mass: 246.22; Observed mass: 247.1 [M+H]+ (RT: 0.6 min).
b) N-(3-amino-5 -(1 H-pyrazol-1 -yl)phenyl)acetamide

To a solution of N-(3-nitro-5-(lH-pyrazol-l-yl)phenyl)acetamide (8.2 g, 33.3
mmol) in ethanol (70 ml) were added iron powder (3.72 g, 66.6 mmol, 2.0 eq.) and 50
% aqueous calcium chloride solution (15 ml). The mixture was stirred at 100 °C for 4 h.
The reaction mixture was quenched with water and extracted with ethyl acetate (3 x 300
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography over silica gel to afford the title compound in 99 %
yield (7.1 g). LC-MS (ESI): Calculated mass: 216.24; Observed mass: 217 [M+H]+ (RT:
0.12 min).
c) N-(3 -((4-bromo-2-nitrophenyl)amino)-5-(l H-pyrazol-1 -yl)phenyl)acetamide
A solution of N-(3-amino-5-(lH-pyrazol-l-yl)phenyl)acetamide (6.97 g, 32.23
mmol), 4-bromo-l-fluoro-2-nitrobenzene (7.09 g, 32.23 mmol, 1.0 eq.) and potassium
fluoride (1.87 g, 32.23 mmol, 1.0 eq.) in DMF was heated at 150 °C for 4 h. The
mixture was quenched with water and extracted with DCM (3 x 100 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure to give the crude residue which was purified by
column chromatography over silica gel to give the title compound in 75 % yield (10 g).
LC-MS (ESI): Calculated mass: 416.23; Observed mass: 417 [M+H]+ (RT: 1.65 min).
d)N-(3-((2-amino-4-bromophenyl)amino)-5-(lH-pyrazol-l-yl)phenyl)acetamide
To a solution of N-(3-((4-bromo-2-nitrophenyl)amino)-5-(l H-pyrazol-1-yl)-
phenyl)acetamide (10 g, 24.03 mmol) in ethanol (70 ml) were added iron powder (2.68
g, 48.05 mmol, 2.0 eq.) and 50 % aqueous calcium chloride solution (20 ml). The
mixture was stirred at 100 °C for 4 h. The mixture was quenched with water and
extracted with ethyl acetate (3 x 100 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was used without purification in the next step.

e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-l-yl)phenyl)acet-
amide
A mixture of N-(3-((2-amino-4-bromophenyl)amino)-5-(lH-pyrazol-l-yl)-
phenyl)acetamide (crude from previous step) and formic acid (20 ml) was heated at 100
°C for 30 min. The formic acid was distilled off under reduced pressure and the crude
was dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 84 % yield (8.0 g). 1H NMR (300 MHz, DMSO-d6): δ 8.72 (s,
1H), 8.57 (d, 1H), 8.22 (m, 1H), 8.11 (s, 1H), 8.01 (d, 1H), 7.87-7.79 (m, 3H), 7.66 (d,
1H), 7.51 (dd, 1H), 6.58 (t, 1H), 2.1 (s, 3H); LC-MS (ESI): Calculated mass: 396.24;
Observed mass: 397 [M+H]+ (RT: 1.38 min).
f) N-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1H-
pyrazol-1 -yl)phenyl)acetamide
A solution of N-(3 -(5 -bromo-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrazol-1 -yl)-
phenyl)acetamide (8.0 g, 20.19 mmol) in 1,2-dimethoxyethane (100 ml) was degassed
by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-
pyrazole (6.3 g, 30.29 mmol, 1.5 eq.) was added and the mixture was degassed for
another 5 min. Pd(PPh3)4 (4.67 g, 4.04 mmol, 0.2 eq.) and aqueous sodium carbonate
(5.35 g, 50.5 mmol, 2.5 eq.) were added sequentially and the mixture was further
degassed for 5 min and then heated at 90 °C for 4 h. The reaction mixture was quenched
with water and extracted with ethyl acetate (3 x 150 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure and the residuewas purified by column chromatography over
silica gel to afford the title compound in 62 % yield (5.0 g). 1H NMR (300 MHz,
CD3OD): δ 9.21 (s, 1H), 8.35 (d, III), 8.13-8.08 (m, 3H), 8.0 (s, 1H), 7.94 (s, 1H), 7.88-
7.76 (m, 4H), 6.73-6.69 (m, 1H), 3.98 (s, 3H), 2.23 (s, 3H), LC-MS (ESI): Calculated
mass: 397.43; Observed mass: 398.1 [M+Hf (RT: 0.26 min).
Example 115.

N-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrazol-
1 -yl)phenyl)methanesulfonamide
a) 3-(5-(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-pyrazol-1 -
yl)aniline
To a solution of N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
5-(lH-pyrazol-l-yl)phenyl)acetamide of Example 114 (4.0 g, 10.06 mmol) in ethanol
(25 ml) was added 20 % aqueous solution of NaOH (5 ml) and the reaction was heated
at 100 °C for 2 h. The reaction mixture was quenched with water and extracted with
ethyl acetate (3 x 150 ml). The combined organic layer was washed with water, brine
and dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 78 % yield (2.8 g).
b) N-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d] imidazol-1 -yl)-5 -(1H-
pyrazol-1 -yl)phenyl)methanesulfonamide
To a solution of 3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(1 H-pyrazol-l-yl)aniline (50 mg, 0.14 mmol) in DCM was added pyridine (22 mg, 0.28
mmol, 2.0 eq.) followed by methanesulfonyl chloride (19 mg, 0.169 mmol, 1.2 eq.). The
mixture was stirred for 1 h, quenched with water and extracted with DCM (3 x 50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the title product in 20 % yield (12 mg). 1H NMR
(300 MHz, CD3OD): δ 8.68 (s, 1H), 8.35 (d, 1H), 8.02 (s, 1H), 7.92 (s, 1H), 7.87 (s,
1H), 7.84-7.81 (m, 1H), 7.77-7.73 (m, 2H), 7.71 (s, 1H), 7.67-7.63 (m, 1H), 7.5-7.48
(m, 1H), 6.58-6.55 (m, 1H), 3.93 (s, 3H), 3.12 (s, 3H); LC-MS (ESI): Calculated mass:
433.49; Observed mass: 434.1 [M+H]+ (RT: 0.35 min).
Example 116.
N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrazol -
l-yl)phenyl)propane-2-sulfonamide

The compound was prepared from the compound of Example 114 using the
procedures described in Example 115. 1H NMR (300 MHz, CD3OD): δ 8.65 (s, 1H),
8.37 (d, 1H), 8.05 (s, 1H), 7.96 (s, 1H), 7.91 (s, 1H), 7.81 (m, 3H), 7.76-7.74 (m, 1H),
7.69-7.67 (m, 1H), 7.55-7.54 (m, 1H), 6.61-6.6 (m, 1H), 3.95 (s, 3H), 3.54-3.49 (m,
1H), 1.43 (d, 6H); LC-MS (ESI): Calculated mass: 461.54; Observed mass: 462.1
[M+H]+ (RT: 0.7 min).
Example 117.
N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrazol-
l-yl)phenyl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 114 using the
procedures described in Example 115. 1H NMR (300 MHz, CD3OD): δ 8.54 (s, 1H),
8.37 (d, 1H), 8.02 (s, 1H), 7.93 (d, 1H), 7.88 (s, 1H), 7.82-7.8 (m, 3H), 7.72 (d, 1H),
7.65-7.62 (m, 1H), 7.53-7.52 (m, 1H), 6.6-6.59 (m, 1H), 3.95 (s, 3H), 2.81-2.78 (m,
1H), 1.18-1.15 (m, 2H), 1.09-1.04 (m, 2H); LC-MS (ESI): Calculated mass: 459.52;
Observed mass: 460.1 [M+H]+ (RT: 0.58 min).
Example 118.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-
1 -yl)phenyl)benzenesulfonamide
The compound was prepared from the compound of Example 114 using the
procedures described in Example 115. }H NMR (300 MHz, CD3OD): δ 9.2 (s, 1H), 8.29
(d, 1H), 8.12 (s, 1H), 8.0 (s, 1H), 7.96-7.93 (m, 3H), 7.83-7.75 (m, 4H), 7.69-7.65 (m,
1H), 7.61-7.54 (m, 3H), 7.45 (t, 1H), 6.58 (m, 1H), 3.98 (s, 3H); LC-MS (ESI):
Calculated mass: 495.56; Observed mass: 496.2 [M+H]+ (RT: 1.28 min).
Example 119
N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1 H-pyrazol-
1 -yl)phenyl)piperidine-l -sulfonamide

The compound was prepared from the compound of Example 114 using the
procedures described in Example 115. *H NMR (300 MHz, CD3OD): δ 8.92 (s, 1H), 8.3
(d, 1H), 8.06 (s, 1H), 8.0 (s, 1H), 7.95 (s, 1H), 7.88 (s, 1H), 7.77-7.69 (m, 5H), 7.45 (m,
1H), 6.56 (m, 1H), 3.92 (s, 3H), 3.28-3.27 (m, 4H), 1.6-1.49 (m, 6H); LC-MS (ESI):
Calculated mass: δ02.59; Observed mass: δ03.1 [M+H]+ (RT: 0.1.33 min).
Example 120.
1 -(furan-2-ylmethyl)-3 -(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-
1 -yl)-5-( 1 H-pyrazol-1 -yl)phenyl)urea
To a solution of 3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(1 H-pyrazol-l-yl)aniline of Example 115(a) (50 mg, 0.141 mmol) in DCM (1 ml) at 0
°C were added TEA (29 mg, 0.281 mmol, 2.0 eq.) and 2-(isocyanatomethyl)furan (21
mg, 0.169 mmol, 1.2 eq.) and the mixture was stirred at room temperature for 16 h. The
solvent was removed under reduced pressure and the residue was purified by preparative
HPLC to afford the title compound in 15 % yield (10 mg). 1H NMR (300 MHz,
CD3OD): δ 9.16 (s, 1H), 8.35 (d, 1H), 8.1 (s, 1H), 8.0 (s, 1H), 7.95-7.94 (m, 2H), 7.91
(m, 1H), 7.87 (d, 1H), 7.8-7.78 (m, 2H), 7.75-7.74 (m, 1H), 7.46 (d, 1H), 6.6-6.59 (m,
1H), 6.38-6.37 (m, 1H), 6.31-6.3 (m, 1H), 4.43 (s, 2H), 3.98 (s, 3H); LC-MS (ESI):
Calculated mass: 478.51; Observed mass: 479.0 [M+H]+ (RT: 0.72 min).
Example 121.
1 -(4-fluorophenyl)-3-(3-(5-( 1 -methyl-1 H-pyrazol-4-yl)-l H-benzo[d]imidazol-1 -
yl)-5 -(1 H-pyrazol-1 -yl)phenyl)urea
The compound was prepared using the procedures described in Example 120. 1H
NMR (300 MHz, CD3OD): S 9.7 (s, 1H), 9.3 (s, 1H), 8.67 (s, 1H), 8.62 (d, 1H), 8.21 (s,
1H), 8.06 (s, 1H), 8.0 (s, 1H), 7.95 (s, 1H), 7.83-7.81 (m, 2H), 7.75-7.71 (m, 2H), 7.63-
7.6 (m, 1H), 7.52-7.49 (m, 2H), 7.15 (t, 2H), 6.61-6.6 (m, 1H), 3.88 (s, 3H); LC-MS
(ESI): Calculated mass: 492.51; Observed mass: 493.2 [M+H]+ (RT: 1.37 min).

Example 122.
N-(3-(5-( 1 H-pyrazol-1 -yl)-l H-benzo[d]iraidazol-1 -yl)-5-( 1 H-pyrazol-1 -yl)-
phenyl)acetamide
To a solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-l-yl)-
phenyl)acetamide of Example 114(e) (200 mg, 0.505 mmol) in DMF (20 ml) were
added pyrazole (41 mg, 0.606 mmol 1.2 eq.), copper(I) oxide (0.7 mg, 0.0051 mmol,
0.01 eq.) and cesium carbonate (329 mg, 1.01 mmol, 2.0 eq.) and the mixture was
heated at 110 °C for 12 h. The reaction mixture was quenched with water and extracted
with ethyl acetate (3 x 25 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 20
% yield (37 mg). 1H NMR (300 MHz, CD3OD): δ 8.9 (br s, 1H), 8.37-8.33 (m, 2H),
8.19 (s, 1H), 8.13-8.12 (m, 1H), 8.06-8.05 (m, 1H), 7.92 (m, 2H), 7.86-7.85 (m, 1H),
7.8-7.78 (m, 2H), 6.61-6.57 (m, 2H), 2.22 (s, 3H); LC-MS (ESI): Calculated mass:
383.41; Observed mass: 384.3 [M+H]+ (RT: 0.52 min).
Example 123.
1 -(3 -(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d] imidazol-1 -yl)-5-( 1 H-pyrazol-1 -
yl)phenyl)-3-(furan-2-ylmethyl)urea
a) 3 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrazol-1 -yl)aniline
To a solution of N-(3-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-
pyrazol-1-yl) phenyl) acetamide of Example 122 (230 mg, 0.6 mmol) in ethanol (20 ml)
was added aqueous solution of sodium hydroxide (192 mg, 4.8 mmol, 8.0 eq.) and the
mixture was heated at 90 °C for 3 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 * 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 73 % yield (150 mg).

b) 1 -(3-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-5-(l H-pyrazol-1 -
yl)phenyl)-3-(furan-2-ylmethyl)urea
To a solution of 3 -(5 -(1 H-pyrazol- l-yl)-lH-benzo [d]imidazol-l -yl)-5-(l H-
pyrazol-l-yl)aniline (50 mg, 0.146 mmol) in DCM was added TEA (45 mg, 0.439
mmol, 3.0 eq.) followed by 2-(isocyanatomethyl)furan (23 mg, 0.19 mmol, 1.3 eq.). The
mixture was stirred for 1 h, quenched with water and extracted with ethylacetate (3 x 20
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by preparative HPLC to give the product in 8 % yield (5 mg). *H NMR (300
MHz, CD3OD): δ 8.92 (br s, 1H), 8.34-8.31 (m, 2H), 8.16 (s, 1H), 7.92-7.89 (m, 4H),
7.77 (m, 2H), 7.71 (m, 1H), 7.44 (m, 1H), 6.57 (m, 2H), 6.36-6.35 (m, 1H), 6.29-6.28
(m, 1H), 4.41 (s, 2H); LC-MS (ESI): Calculated mass: 464.48; Observed mass: 465.2
[M+H]+(RT: 1.35 min).
Example 124.
1 -(3-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1 H-pyrazol-1 -yl)-
phenyl)-3-cyclopentylurea
The compound was prepared from the compound of Example 122 using the
procedures described in Example 123. 1H NMR (300 MHz, CD3OD): δ 9.21 (br s, 1H),
8.35-8.33 (m, 2H), 8.22 (s, 1H), 7.98 (s, 2H), 7.93-7.88 (m, 2H), 7.78-7.77 (m, 2H),
7.73-7.72 (m, 1H), 6.59-6.58 (m, 2H), 4.08 (m, 1H), 1.99-1.96 (m, 2H), 1.75-1.71 (m,
2H), 1.68-1.33 (m, 2H), 1.52-1.49 (m, 2H); LC-MS (ESI): Calculated mass: 452.51;
Observed mass: 453.3 [M+H]+ (RT: 1.42 min).
Example 125.
N-(3-(5-( 1 H-imidazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-5-( 1 H-pyrazol-1 -yl)-
phenyl)acetamide
The compound was prepared from the compound of Example 114(e) using the
procedures described in Example 122. 1H NMR (300 MHz, CD3OD): δ 9.43 (s, 1H),

8.77 (s, 1H), 8.35 (d, 2H), 8.16 (m, 1H), 8.12 (s, 1H), 8.09-8.08 (m, 1H), 8.03-8.02 (m,
1H), 8.0 (s, 1H), 7.98 (s, 1H), 7.83-7.82 (m, 1H), 7.79-7.72 (m, 3H), 6.59-6.58 (m, 1H),
2.21 (s, 3H); LC-MS (ESI): Calculated mass: 383.41; Observed mass: 384.1 [M+H]+
(RT:0.12min).
Example 126.
N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5-( 1 H-pyrazol-
1 -yl)phenyl)ethanesulfonamide
The compound was prepared from the compound of Example 114 using the
procedures described in Example 115. [H NMR (400 MHz, CD3OD): δ 9.13 (s, 1H),
8.36 (d, 1H), 8.10 (s, 1H), 8.02 (s, 1H), 7.94 (s, 1H), 7.88-7.78 (m, 5H), 7.58 (s, 1H),
6.61-6.50 (m, 1H), 3.97 (s, 3H), 3.31 (quartet, 2H) 1.40 (t, 3H); LC-MS (ESI):
Calculated mass: 447.51; Observed mass: 448.1 [M+H]+ (RT: 0.49 min).
Example 127.
N-(3-(5-( 1 -(cyclopropylmethyl)-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -
(II I-pyrazol-1 -yl)phenyl)acetamide
A solution of N-(3 -(5 -bromo-1 H-benzo [d] imidazol-1 -yl)-5 -(1 H-pyrazol-1 -yl)-
phenyl)acetamide of Example 114(e) (0.5 g, 1.26 mmol) in 1,2-dimethoxyethane (10
ml) was degassed by N2 bubbling for 5 min. l-(Cyclopropylmethyl)-4-(4,4,5,5-tetra-
methyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole of Intermediate Example 9 (0.47 g, 1.89
mmol, 1.5 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2
(0.2 g, 0.25 mmol. 0.2 eq.) and aqueous sodium carbonate (0.27 g, 2.52 mmol, 2 eq.)
were added sequentially and the mixture was further degassed for 5 min followed by
heating at 90 °C for 4 h. The reaction mixture was quenched with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 11
% yield (60 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.52 (s, 1H), 8.82-8.73 (m, 1H),
8.59 (d, 1H), 8.23-8.15 (m, 3H), 8.03-7.92 (m, 2H), 7.83-7.74 (m, 2H), 7.72-7.59 (m,

2H), 6.59 (s, 1H), 4.23 (d, 2H), 2.12 (s, 3H), 1.25-0.78 (m, 5H); LC-MS (EST):
Calculated mass: 437.50; Observed mass: 438.2 [M+H]+ (RT: 0.812 min).
Example 128.
N-(3 -(5 -(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(1H-
pyrazol-1 -yl)phenyl)acetamide
a) tert-butyi 4-(4-( 1 -(3-acetamido-5-( 1 H-pyrazol-1 -yl)phenyl)-1 H-benzo[d]-
imidazol-5-yl)-1 H-pyrazol-1 -yl)piperidine-1 -carboxylate
A solution of N-(3-(5-bromo-1 H-benzo[d]imidazol-1 -yl)-5-(lH-pyrazol-1 -yl)-
phenyl)acetamide of Example 114(e) (0.6 g, 1.51 mmol) in 1,2-dimethoxyethane (20
ml) was degassed by N2 bubbling for 5 min. ter/-Butyl 4-(4-(4,4,5,5-tetramethyl-l,3,2-
dioxaborolan-2-yl)-lH-pyrazol-l-yl)piperidine-l-carboxylate of Intermediate Example 5
(0.85 g, 2.27 mmol, 1.5 eq.) was added and the mixture was degassed for another 5 min.
Pd(dppf)Cl2 (0.25g, 0.302 mmol, 0.2 eq.) and aqueous sodium carbonate (0.5 g, 4.53
mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min
followed by heating at 100 °C for 4 h. The reaction mixture was quenched with water
and extracted with ethyl acetate (3 x 20 ml). The combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure and the residue was purified by preparative HPLC to give the title
product in 35 % yield (0.3 g).
b)N-(3-(5-(l-(piperidin-4-yl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(1 H-pyrazol-1 -yl)phenyl)acetamide
To a solution of ter/-butyl 4-(4-(l-(3-acetamido-5-(lH-pyrazol-l-yl)phenyl)-lH-
benzo[d]imidazol-5-yl)-lH-pyrazol-l-yl)piperidine-l-carboxylate (300 mg, 0.53 mmol)
in DCM (4 ml) at 0 °C was added trifluoroacetic acid (0.6 ml) and the mixture was
stirred at room temperature for 6 h. The solvent was distilled off under reduced pressure
and the residue was purified by preparative HPLC to give the title product in 89 % yield
(220 mg). 1HNMR (300 MHz, DMSO-d6): δ 10.50 (s, 1H), 8.84 (s, 1H), 8.73 -8.63 (m,

1H), 8.61 (d, 1H), 8.52-8.38 (m, 1H), 8.35 (s, 1H), 8.20 (s, 1H), 8.07 (d, 1H), 8.01 (s,
1H), 7.87-7.83 (m, 2H), 7.73-7.65 (m, 2H), 6.62 (t, 1H), 4.36 (m, 1H), 3.50-3.35 (m,
2H), 3.17-3.10 (m, 2H), 2.32-2.21 (m, 4H), 2.14 (s, 3H); LC-MS (ESI): Calculated
mass: 466.54; Observed mass: 467.2 [M+H]+ (RT: 0.128 min).
Example 129.
N-(3-(5-(l-(l-(methylsulfonyl)piperidin-4-yl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)-5 -(1 H-pyrazol-1 -yl)phenyl)acetamide
To a solution of N-(3-(5-(l-(piperidin-4-yl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)-5-(lH-pyrazol-1-yl)phenyl)acetamide (Example 128) (80 mg, 0.171
mmol) in DCM (10 ml) was added pyridine (27 mg, 0.34 mmol, 2 eq.) and methane-
sulfonyl chloride (19 mg, 0.171 mmol, 1 eq.). The mixture was stirred for 4 h, quenched
with water and extracted with DCM (3 x 50 ml). The solvent was distilled off under
reduced pressure and the residue was purified by preparative HPLC to give the title
product in 19 % yield (18 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.52 (s, 1H), 10.06
(s, 1H), 8.58 (d, 1H), 8.43 (s, 1H), 8.24 (s, 1H), 8.06-8.00 (m, 3H), 7.89 (s, 1H), 7.83 (d,
1H), 7.78-7.74 (m, 2H), 6.62 (t, 1H), 4.36 (m, 1H), 3.01-2.94 (m, 6H), 2.30 (s, 3H), 2.13
(s, 3H), 2.10-2.01 (m, 2H); LC-MS (ESI): Calculated mass: δ44.63; Observed mass: δ45.2 [M+H]+(RT: 0.40 min).
Example 130.
N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-l-yl)phenyl)-
acetamide
a) N-(3-(4-formyl-2-nitrophenylamino)-5-(lH-pyrazol-1 -yl)phenyl)acetamide
A solution of N-(3 -amino-5-(l H-pyrazol-1-yl)phenyl)acetamide of Example
114(b) (0.35 g, 1.62 mmol), 4-fluoro-3-nitrobenzaldehyde (0.24 g, 1.62 mmol, 1.0 eq.)
and potassium fluoride (94 mg, 1.62 mmol, 1.0 eq.) in DMF (2 ml) was heated at 130 °C
for 4 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over

sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in
hexane) to give the title product in 51 % yield (0.3 g). *H NMR (300 MHz, DMSO-d6): δ 10.29 (s, 1H), 10.03 (s, 1H), 9.87 (s, 1H), 8.71 (m, 1H), 8.43 (d, 1H), 8.05 (s, 1H),
7.92 (d, 1H), 7.76 (s, 1H), 7.60 (s, 1H), 7.54 (s, 1H), 7.27 (s, 1H), 6.55 (s, 1H), 2.10 (s,
3H).
b) N-(3 -(2-nitro-4-(oxazol-4-yl)phenylamino)-5-( 1 H-pyrazol-1 -yl)phenyl)-
acetamide
To a solution of N-(3-(4-formyl-2-nitrophenylamino)-5-(lH-pyrazol-l-yl)-
phenyl)acetamide (0.3 g, 0.824 mmol) in methanol (8 ml) was added potassium
carbonate (0.18 g, 0.904 mmol, 1.1 eq.) and the mixture was stirred for 10 min at room
temperature. Toluenesulfonylmethyl isocyanide (0.124 g, 0.904 mmol, 1.1 eq.) was
added and the mixture was refluxed for 4 h. The solvent was distilled off and water was
added to the crude. The r mixture was extracted with ethyl acetate (3 x 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to give the
title product in 75 % yield (0.25 g). lH NMR (300 MHz, DMSO-d6): δ 10.23 (s, 1H),
9.57 (s, 1H), 8.46-8.40 (m, 3H), 7.94-7.89 (m, 2H), 7.76-7.72 (m, 2H), 7.57 (s, 1H),
7.49 (s, 1H), 7.42 (d, 1H), 6.55 (t, 1H), 2.01 (s, 3H).
c)N-(3-(2-amino-4-(oxazol-4-yl)phenylamino)-5-(lH-pyrazol-l-yl)phenyl)-
acetamide
To a solution of N-(3-(2-nitro-4-(oxazol-4-yl)phenylamino)-5-(l H-pyrazol-1-yl)-
phenyl)acetamide (0.25 g, 0.62 mmol) in methanol (15 ml) and ethyl acetate (7 ml) was
added 10 % Pd/C (30 mg) and the reaction vessel was purged with nitrogen gas for 5
min. The mixture was then hydrogenated with H2 balloon for 4 h. The mixture was
filtered through a pad of celite and the filtrate was concentrated under reduced pressure
to afford the title compound in 86 % yield (0.2 g).

d)N-(3-(5-(oxazol-5-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrazol-l-yl)phenyl)-
acetamide
A mixture of N-(3-(2-ammo-4-(oxazol-4-yl)phenylammo)-5-(lH-pyrazol-l -yl)-
phenyl)acetamide (0.2 g, 0.54 mmol) and formic acid (3 ml) was heated at 100 °C for 30
min. The formic acid was distilled off under reduced pressure and the residue was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by preparative HPLC to give the title product in 6 % yield (12 mg).
1H NMR (300 MHz, DMSO-<50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 20 % yield (20 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.4 (s, 1H),
8.64 (s, 1H), 8.20 (s, 1H), 8.07 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.8-7.68 (m, 2H), 7.6-

7.45 (m, 4H), 7.27 (t, 1H), 3.88 (s, 3H), 2.12 (s, 3H); LC-MS (ESI): Calculated mass:
443.45; Observed mass: 444.1 [M+Hf (RT: 1.147 min).
Example 139.
N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-p>Tazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)biphenyl-3-yl)acetamide
A solution of iV-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',5'-difluorobiphenyl-
3-yl)acetamide of Example 138(e) (5 g, 11.34 mmol) in 1,2-dimethoxyethane (100 ml)
was degassed by N2 bubbling for 5 min. 4-(2-(4-(4,4,5,5-Tetramethyl-l,3,2-dioxa-
borolan-2-yl)-lH-pyrazol-l-yl)ethyl)morpholine (4.2 g, 13.61 mmol, 1.2 eq.) was added
and the mixture was degassed for another 5 min. Pd(PPli3)4 (1.3 g, 1.13 mmol, 0.1 eq.)
and aqueous sodium carbonate (2.4 g, 22.67 mmol, 2.0 eq.) were added sequentially and
the mixture was further degassed for 5 min and then heated at 90 °C for 3 h. The
mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
preparative HPLC to give the title product in 37 % yield (2.3 g). 1H NMR (400 MHz,
DMSO-d6): δ 10.42 (s, 1H), 8.87 (s, 1H), 8.34 (s, 1H), 8.17 (s, 1H), 8.13 (s, 1H), 8.05
(s, 1H), 7.80-7.53 (m, 2H), 7.66-7.58 (m, 3H), 7.46-7.44 (m, 1H), 7.38-7.32 (m, 1H),
4.59 (t, 2H), 3.76-3.67 (m, 4H), 3.43-3.39 (m, 2H), 2.54-2.44 (m, 4H), 2.07 (s, 3H); LC-
MS (ESI): Calculated mass: δ42.58; Observed mass: δ43.3 [M+H]+ (RT: 0.22 min).
Example 140.
N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-yl)methanesulfonamide
a) 2',5'-difluoro-5-(5-( 1 -(2-morpholinoethyl)-1 H-pyrazol-4-yl)-1 H-benzo[d]-
imidazol-1 -yl)biphenyl-3 -amine
To a solution of N-(2\5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-
lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)acetarnide of Example 139 (2.2 g, 4.0 mmol)

in ethanol (100 ml) was added aqueous solution of NaOH (2.0 g, 50 mmol, 12.5 eq.) and
the mixture was heated at 100 °C for 4 h. The reaction mixture was quenched with water
and extracted with ethyl acetate (3 * 100 ml). The combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure to afford the title product in 90 % yield (1.8 g).
b)N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)biphenyl-3-yl)methanesulfonamide
To a solution of 2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-
benzo[d]imidazol-l-yl)biphenyl-3-amine (100 mg, 0.2 mmol) in DCM (2 ml) was added
pyridine (32 mg, 0.4 mmol, 2.0 eq.) followed by methanesulfonyl chloride (30 mg, 0.26
mmol, 1.3 eq.). The mixture was stirred for 1 h, quenched with water and extracted with
DCM (3 x 50 ml). The combined organic layer was washed with water, brine and dried
over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by preparative HPLC to give the title product in 26 % yield (30
mg). 1H NMR (400 MHz, CD3OD): δ 9.34 (s, 1H), 8.25 (s, 1H), 8.06-8.05 (m, 2H),
7.86.7.80 (s, 2H), 7.74-7.73 (m, 1H), 7.68 (m, 1H), 7.60-7.59 (m, 1H), 7.44-7.39 (m,
1H), 7.33-7.27 (m, 1H), 7.24-7.19 (m, 1H), 4.69 (t, 2H), 3.94-3.88 (m, 4H), 3.76 (t, 2H),
3.54-3.40 (m, 4H), 3.19 (s, 3H); LC-MS (ESI): Calculated mass: δ78.63; Observed
mass: δ79.3 [M+H]+ (RT: 0.26 min).
Example 141.
N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)biphenyl-3-yl)ethanesulfonamide
The compound was prepared from the compound of Example 139 using the
procedures described in Example 140. *H NMR (400 MHz, DMSO-c?6): δ 10.34 (s, 1H),
8.69 (s, 1H), 8.27 (s, 1H), 8.01 (s, 1H), 7.98 (s, 1H), 7.72-7.61 (m, 5H), 7.51-7.44 (m,
2H), 7.39-7.35 (m, 1H), 4.27 (t, 2H), 3.58 (t, 4H), 3.32-3.28 (m, 2H), 2.77 (t, 2H), 2.45
(m, AH), 1.22 (t, 3H); LC-MS (ESI): Calculated mass: δ92.66; Observed mass: δ93.2
[M+H]+ (RT: 0.332 min).

Example 142.
N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-p>Tazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)biphenyl-3-yl)propane-2-sulfonamide
The compound was prepared from the compound of Example 139 using the
procedures described in Example 140. 1HNMR (400 MHz, DMSO-d6): δ 10.35 (s, 1H),
8.79 (s, 1H), 8.37 (s, 1H), 8.15 (s, 1H), 8.07 (s, 1H), 7.74-7.62 (m, 5H), 7.54 (s, 1H),
7.51-7.45 (m, 1H), 7.41-7.35 (m, 1H), 4.61 (t, 2H), 3.70-3.63 (m, 6H), 3.52-3.42 (m,
3H), 3.40-3.28 (m, 2H), 1.43 (d, 6H); LC-MS (ESI): Calculated mass: 606.69;
Observed mass: 607.4 [M+H]+ (RT: 0.55 min).
Example 143.
N-(2',5'-difluoro-5-(5-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1-yl)biphenyl-3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 139 using the
procedures described in Example 140. 1H NMR (400 MHz, DMSO-d6): δ 10.31 (s, 1H),
8.76 (s, 1H), 8.36 (s, 1H), 8.14 (s, 1H), 8.07 (s, 1H), 7.73 (d, 1H), 7.67-7.63 (m, 4H),
7.55 (s, 1H), 7.50-7.45 (m, 2H), 4.60 (t, 2H), 3.99-3.79 (m, 2H), 3.69-3.63 (m, 6H),
3.20-3.17 (m, 2H), 2.91-2.88 (m, 1H), 1.1-1.0 (d, 4H); LC-MS (ESI): Calculated mass:
604.67; Observed mass: 605.4 [M+H]+ (RT: 0.48 min).
Example 144.
N-(5-(5-(l-(2-(dimethylamino)ethyl)-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)-2', 5 '-difluorobiphenyl-3 -yl)acetamide
The compound was prepared from the compound of Example 138(e) using the
procedures described in Example 139. 1H NMR (400 MHz, DMSO-d6): δ 10.42 (s, 1H),
8.74 (s, 1H), 8.34 (s, 1H), 8.16 (s, 1H), 8.12 (s, 1H), 8.04 (s, 1H), 7.79-7.73 (m, 2H),
7.64-7.57 (m, 3H), 7.45-7.42 (m, 1H), 7.36-7.34 (m, 1H), 4.56 (t, 2H), 3.62 (t, 2H), 3.84

(s, 6H), 2.12 (s, 3H); LC-MS (ESI): Calculated mass: δ00.54; Observed mass: δ01.2
[M+H]+ (RT: 0.22 min).
Example 145.
N-(5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',5'-difluorobiphenyl-3 -
yl)acetamide
To a solution of ^-(S-^-bromo-lH-benzofdJimidazol-l-yl^^'-difluorobi-
phenyl-3-yl)acetamide of Example 138(e) (2.5 g, 5.67 mmol, 1 eq.) in DMF (10 ml)
were added pyrazole (0.77 g, 11.3 mmol, 2 eq.), copper(I) oxide (1.62 g, 11.3 mmol, 2.0
eq.) and cesium carbonate (3.67 g, 11.3 mmol, 2.0 eq.) and the mixture was heated at 90
°C for 48 h. The reaction mixture was quenched with water and extracted with ethyl
acetate (3 * 100 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by preparative HPLC to give the title product in 79 % yield (1.92
g). 1H NMR (400 MHz, CD3OD): δ 10.43 (s, 1H), 8.84 (s, 1H), 8.60 (d, 1H), 8.24 (s,
1H), 8.12 (s, 1H), 7.97-7.82 (m, 3H), 7.76 (s, 1H), 7.63-7.60 (m, 2H), 7.49-7.32 (m,
1H), 6.56 (s, 1H), 2.10 (s, 3H); LC-MS (ESI): Calculated mass: 429.42; Observed mass:
430.2 [M+H]+(RT: 1.45 min).
Example 146.
N-(5-(5-( 1 H-pyrrol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',5'-difluorobiphenyl-3-
yl)acetamide
To a solution ofA/-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',5'-difluorobi-
phenyl-3-yl)acetamide of Example 138(e) (250 mg, 0.57 mmol, 1 eq.) in DMF (1 ml)
were added pyrazole (77 mg, 1.13 mmol, 2 eq.), copper(I) oxide (162 mg, 1.13 mmol,
2.0 eq.) and cesium carbonate (367 mg, 1.13 mmol, 2.0 eq.) and the mixture was heated
at 90 °C for 48 h. The mixture was quenched with water and extracted with ethyl acetate
(3 x 50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by preparative HPLC to give the title product in 45 % yield (110 mg). 1H

NMR (400 MHz, DMSO-d6): δ 10.45 (s, 1H), 8.81 (s, 1H), 8.15 (s, 1H), 8.00 (d, 1H),
7.86-7.80 (m, 2H), 7.66-7.62 (m, 3H), 7.46-7.44 (m, 4H), 6.29 (t, 2H), 2.13 (s, 3H); LC-
MS (ESI): Calculated mass: 428.43; Observed mass: 429.1 [M+H]+ (RT: 1.647 min).
Example 147.
N-(3-(benzofuran-2-yl)-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-
1 -yl)phenyl)acetamide
a) N-(3 -(benzofuran-2-yl)-5-nitrophenyl)acetamide
A solution of N-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (2 g, 7.7
mmol) in 1,2-dimethoxyethane (25 ml) was degassed by N2 bubbling for 5 min. 2-
(Beiizofuran-2-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (2.45 g, 10 mmol, 1.3 eq.)
was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.63 g, 0.77
mmol, 0.1 eq.) and aqueous sodium carbonate (2.45 g, 23.1 mmol, 3.0 eq.) were added
sequentially and the mixture was further degassed for 5 min followed by heating at 90
°C for 4 h. The reaction mixture was quenched with water and extracted with ethyl
acetate (3 x 50 ml). The combined organic layer was washed with water, brine and dried
over sodium sulphate. The solvent was distilled off under reduced pressure to afford the
crude product which was directly used for the next step.
b)N-(3-amino-5-(benzofuran-2-yl)phenyl)acetamide
To a solution of ^^-(benzomran^-yty-S-nitrophenytyacetamide (1.8 g, 6.08
mmol) in ethanol (30 ml) were added calcium chloride (1.35 g, 12.16 mmol, 2 eq.) and
iron powder (0.7 g, 12.16 mmol, 2 eq.) and the mixture was heated at 100 °C for 2 h and
filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 * 100
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (100-200 neutral alumina, 4 % methanol in
chloroform) to give the title product in 90 % yield (1.45 g).

c)N-(3-(benzofuran-2-yl)-5-(4-bromo-2-nitrophenylamino)phenyl)acetamide
A solution ofN-(3-amino-5-(benzofuran-2-yl)phenyl)acetamide (1.45 g, 5.45
mmol), 4-bromo-l-fluoro-2-nitrobenzene (1.2 g, 5.45 mmol, 1.0 eq.) and potassium
fluoride (0.32 g, 5.45 mmol 1.0 eq.) in DMF (5 ml) was heated at 100 °C for 12 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to
give the title product in 59 % yield (1.5 g).
d)N-(3-(2-amino-4-bromophenylamino)-5-(benzofuran-2-yl)phenyl)acetamide
To a solution of N-(3-(benzofuran-2-yl)-5-(4-bromo-2-nitrophenylamino)-
phenyl)acetamide (1.45 g, 3.12 mmol) in ethanol (35 ml) were added calcium chloride
(0.69 g, 6.24 mmol, 2 eq.) and iron powder (0.36 g, 6.24 mmol, 2 eq.) and the mixture
was heated at 100 °C for 2 h and filtered. The filtrate was diluted with water and
extracted with ethyl acetate (3 x 100 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was directly used for the next step.
e) N-(3-(benzofuran-2-yl)-5-(5-bromo-lH-benzo[d]imidazol-l-yl)phenyl)acet-
amide
A mixture of A-(3-(2-amino-4-bromophenylamino)-5-(benzofuran-2-yl)phenyl)-
acetamide (1.36 g, 3.2 mmol) and formic acid (2 ml) was heated at 100°C for 30 min.
The formic acid was distilled off under reduced pressure and the residue was dissolved
in ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 61 % yield (0.85 g).

f) N-(3 -(benzofuran-2-yl)-5-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]-
imidazol-1 -yl)phenyl)acetamide
A solution of A^-(3-(benzofuran-2-yl)-5-(5-bromo-lH-benzo[d]imidazol-l-yl)-
phenyl)acetamide (0.8 g, 1.8 mmol) in 1,2-dimethoxyethane (20 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-
zole (0.56 g, 2.7 mmol, 1.5 eq.) was added and the mixture was degassed for another 5
min. Pd(PPh3)4 (0.207 g, 0.18 mmol, 0.1 eq.) and aqueous sodium carbonate (3.8 g, 3.6
mmol, 2.0 eq.) were added sequentially and the mixture was further degassed for 5 min
and then heated at 90 °C for 3 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the pure product in
75 % yield (0.6 g). 1H NMR (300 MHz, DMSO-d6): δ 10.46 (s, 1H), 8.78 (s, 1H), 8.21
(m, 2H), 8.06 (s, 1H), 8.01 (s, 1H), 7.96 (s, 2H), 7.74-7.64 (m, 3H), 7.63-7.59 (m, 2H),
7.34-7.31 (m, 2H), 3.89 (s, 3H), 2.15 (s, 3H); LC-MS (ESI): Calculated mass: 447.49;
Observed mass: 448.1 [M+H]+ (RT: 1.397 min).
Example 148.
N-(5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)-
acetamide
a) iV-(5-nitrobiphenyl-3-yl)acetamide
A solution of A^-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (1 g, 3.87
mmol) in 1,2-dimethoxyethane (20 ml) was degassed by N2 bubbling for 5 min. Phenyl-
boronic acid (0.61 g, 5.04 mmol, 1.3 eq.) was added and the mixture was degassed for
another 5 min. Pd(dppf)Cl2 (0.63 g, 0.77 mmol, 0.2 eq.) and aqueous sodium carbonate
(1.23 g, 11.6 mmol, 3.0 eq.) were added sequentially and the reaction mixture was
further degassed for 5 min and then heated at 90 °C for a period of 2 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.

The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 61 % yield (0.6 g).
b)N-(5-aminobiphenyl-3-yl)acetamide
To a solution of N-(5-nitrobiphenyl-3-yl)acetamide (1.2 g, 4.68 mmol) in THF
(10 ml) were added a solution of ammonium chloride (2 g, 37.4 mmol, 8 eq.) in water (2
ml) and zinc (2.36 g, 37.4 mmol, 8 eq.). The reaction mixture was stirred at 45 °C for 2
h and filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 x
100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 94 % yield (1 g).
c)N-(5-(4-bromo-2-nitrophenylamino)biphenyl-3-yl)acetamide
A solution of N-(5-aminobiphenyl-3-yl)acetamide (1 g, 4.54 mmol), 4-bromo-l-
fluoro-2-nitrobenzene (1.03 g, 4.54 mmol, 1.0 eq.) and potassium fluoride (0.26 g, 4.54
mmol, 1.0 eq.) in DMF (5 ml) was heated at 100 °C for 12 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 100 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the title
product in 52 % yield (1 g).
d)N-(5-(2-amino-4-bromophenylamino)biphenyl-3-yl)acetamide
To a solution of N-(5-(4-bromo-2-nitrophenylamino)biphenyl-3-yl)acetamide
(1.0 g, 2.35 mmol) in THF (10 ml) were added a solution of ammonium chloride (1.18
g, 18.8 mmol, 8 eq.) in water (2 ml) and zinc (1 g, 18.8 mmol, 8 eq.). The mixture was
stirred at 45 °C for 2 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,

brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 43 % yield (0.4 g).
e)N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)acetamide
A mixture of N-(5-(2-amino-4-bromophenylamino)biphenyl-3-yl)acetamide (0.4
g, 1.01 mmol) and formic acid (10 ml) was heated at 100 °C for 2 h. The formic acid
was distilled off under reduced pressure and the crude was dissolved in ethyl acetate.
The ethyl acetate layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 85 % yield (0.35 g).
f) N-(5-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)biphenyl-3 -yl)-
acetamide
A solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)biphenyl-3-yl)acetamide
(400 mg, 0.99 mmol) in 1,2-dimethoxyethane (10 ml) was degassed by N2 bubbling for
5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (220 mg,
1.05 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min.
Pd(PPh3)4 (230 mg, 0.197 mmol, 0.2 eq.) and aqueous sodium carbonate (320 mg, 3.01
mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min
and then heated at 90 °C for 3 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 12
% yield (50 mg). ]H NMR (300 MHz, DMSO-d6): δ 10.36 (s, 1H), 8.68 (s, 1H), 8.18 (s,
1H), 8.02-7.97 (m, 2H), 7.93-7.88 (m, 2H), 7.75-7.67 (s, 3H), 7.61-7.49 (m, 4H), 7.43
(t, 1H), 3.87 (s, 3H), 2.12 (s, 3H); LC-MS (ESI): Calculated mass: 407.47; Observed
mass: 408.1 [M+H]+ (RT: 1.67 min).
Example 149.

N-(4'-methoxy-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)bi-
phenyl-3 -yl)acetamide
a)N-(4'-methoxy-5-nitrobiphenyl-3-yl)acetamide
A solution of N-^-bromo-S-nitrophenyOacetamide of Example 1(c) (1 g, 3.8
mmol) in 1,2-dimethoxyethane (20 ml) was degassed by N2 bubbling for 5 min. 4-
Methoxyphenylboronic acid (0.69 g, 4.4 mmol, 1.1 eq.) was added and the mixture was
degassed for another 5 min. Pd(dppf)Cl2 (0.31 g, 0.38 mmol, 0.1 eq.) and aqueous
sodium carbonate (1 g, 9.5 mmol, 2.5 eq.) were added sequentially and the mixture was
further degassed for 5 min and then heated at 90 °C for 2 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to give the title
product in 73 % yield (0.8 g).
b)N-(5-amino-4'-methoxybiphenyl-3-yl)acetamide
To a solution of N-(4'-methoxy-5-nitrobiphenyl-3-yl)acetamide (4 g, 13.98
mmol) in ethanol (50 ml) were added calcium chloride (3.1 g. 27.96 mmol, 2 eq.) and
iron powder (1.45 g, 27.96 mmol, 2 eq.) and the mixture was heated at 100 °C for 2 h
and filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 * 100
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure to afford the product in
87% yield (3.1 g).
c)N-(5-(4-bromo-2-nitrophenylamino)-4'-methoxybiphenyl-3-yl)acetamide
A solution of N-(5-amino-4'-methoxyhiphenyl-3-yl)acetamide (3.1 g, 12.11
mmol), 4-bromo-l-fluoro-2-nitrobenzene (2.66 g, 12.11 mmol, 1.0 eq.) and potassium
fluoride (0.7 g, 12.11 mmol, 1.0 eq.) in DMF (5 ml) was heated at 100 °C for 12 h. The

reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 40 % ethyl acetate.in hexane) to
yield the title product in 52% yield (2.9 g).
d)N-(5-(2-amino-4-bromophenylamino)-4'-methoxybiphenyl-3-yl)acetamide
To a solution of N-(5-(4-bromo-2-nitrophenylamino)-4'-methoxybiphenyl-3-yl)-
acetamide (2.9 g, 6.37 mmol) in ethanol (30 ml) were added calcium chloride (1.4 g,
12.74 mmol, 2 eq.) and iron powder (0.66 g, 12.74 mmol, 2 eq.) and the mixture was
heated at 100 °C for 2 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the crude residue which was directly used for the next step.
e)N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-methoxybiphenyl-3-yl)acet-
amide
A mixture ofN-(5-(2-amino-4-bromophenylamino)-4'-methoxybiphenyl-3-
yl)acetamide (2.7 g, 6.37 mmol) and formic acid (2 ml) was heated at 100 °C for 30 min.
The formic acid was distilled off under reduced pressure and the crude was dissolved in
ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 79 % yield (2.2 g).
f)N-(4'-methoxy-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)bi-
phenyl-3 -yl)acetamide
A solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-methoxybiphenyl-3-
yl)acetamide (0.8 g, 1.84 mmol) in 1,2-dimethoxyethane (8 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-

zole (0.5 g, 2.4 mmol, 1.3 eq.) was added and the mixture was degassed for another 5
min. Pd(PPh3)4 (0.212 g, 0.184 mmol, 0.1 eq.) and aqueous sodium carbonate (0.39 g,
3.68 mmol, 2.0 eq.) were added sequentially and the mixture was further degassed for 5
min and then heated at 90 °C for 3 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product in 67
% yield (0.54 g). JH NMR (300 MHz, DMSO-dQ: δ 8.48 (s, 1H), 7.96-7.84 (m, 4H),
7.74-7.45 (m, 7H), 7.01 (d, 2H), 3.93 (s, 3H), 3.83 (s, 3H), 2.19 (s, 3H); LC-MS (ESI):
Calculated mass: 437.49; Observed mass: 437.9 [M+H]+ (RT: 0.89 min).
Example 150.
N-(3',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)bi-
phenyl-3 -yl)acetamide
a)N-(3',4'-difluoro-5-nitrobiphenyl-3-yl)acetamide
A solution of Af-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (0.7 g, 2.69
mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. 3,4-
Difluorophenylboronic acid (0.5 g, 3.23 mmol, 1.2 eq.) was added and the mixture was
degassed for another 5 min. Pd(dppf)Cl2 (0.44 g, 0.54 mmol, 0.2 eq.) and aqueous
sodium carbonate (0.86 g, 8.07 mmol, 3.0 eq.) were added sequentially and the mixture
was further degassed for 5 min and then heated at 100 °C for 5 h. The reaction mixture
was quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 25 % ethyl acetate in hexane) to give the title
product in 76 % yield (0.6 g).
b)N-(5-amino-3',4'-difluorobiphenyl-3-yl)acetamide

To a solution of yV-(3',4'-difluoro-5-nitrobiphenyl-3-yl)acetamide (0.6 g, 2.05
nxmol) in methanol (10 ml) and ethyl acetate (2 ml) was added 10 % Pd/C (100 mg) and
the reaction vessel was purged with nitrogen gas for 5 min. The mixture was then
hydrogenated with H2 balloon for 12 h. The mixture was filtered through a pad of celite
and the filtrate was concentrated under reduced pressure to afford the title compound in
93 % yield (0.5 g).
c)N-(5-(4-bromo-2-nitrophenylamino)-3',4'-difluorobiphenyl-3-yl)acetamide
A solution ofN-(5-amino-3',4'-difluorobiphenyl-3-yl)acetamide (0.5 g, 1.9
mmol), 4-bromo-l-fluoro-2-nitrobenzenc (0.42 g, 1.9 mmol, 1.0 eq.) and potassium
fluoride (0.11 g, 1.9 mmol, 1.0 eq.) in DMF was heated at 130 °C for 5 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 * 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 57 % yield (0.5 g). 1HNMR (300 MHz, DMSO-d6): δ 10.16 (s, 1H),
9.43 (s, 1H), 8.23 (d, 1H), 7.69-7.58 (m, 3H), 7.41-7.38 (m, 2H), 7.29-7.26 (m, 2H),
7.19 (s,lH), 2.04 (s,3H).
d)N-(5-(2-amino-4-bromophenylamino)-3',4'-difluorobiphenyl-3-yl)acetamide
To a solution of N-(5-(4-bromo-2-nitrophenylamino)-3',4'-difluorobiphenyl-3-
yl)acetamide (0.5 g, 1.08 mmol) in THF (10 ml) were added a solution of ammonium
chloride (0.46 g, 8.67 mmol, 10 eq.) in water (2 ml) and zinc (0.57 g, 8.67 mmol, 8 eq.).
The mixture was stirred at room temperature for 6 h and filtered. The filtrate was diluted
with water and extracted with ethyl acetate (3 x 100 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure to afford the title product in 86 % yield (0.4 g).
e)N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-3',4'-difluorobiphenyl-3-yl)acet-
amide

A mixture of iV-(5-(2-amino-4-bromophenylamino)-3',4'-difluorobiphenyl-3-yl)-
acetamide (0.4 g, 0.93 mmol) and formic acid (5 ml) was heated at 100 °C for 30 min.
The formic acid was distilled off under reduced pressure and the caide was dissolved in
ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 97 % yield (0.4 g).
f)A'-(3,,4'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3-yl)acetamide
A solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-3',4'-difluorobiphenyl-
3-yl)acetamide (0.1 g, 0.226 mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-
zole (0.057 g, 0.271 mmol, 1.2 eq.) was added and the mixture was degassed for another
5 min. Pd(dppf)Ci2 (0.037 g, 0.045 mmol, 0.2 eq.) and aqueous sodium carbonate (0.072
g. 0.678 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed
for 5 min and then heated at 100 °C for 5 h. The reaction mixture was quenched with
water and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by column chromatography (60-120
silica gel, 80 % ethyl acetate in hexane) to give the title product in 30 % yield (30 mg).
1H NMR (300 MHz, DMSO-d6): δ 10.43 (s, 1H), 9.03 (s, 1H), 8.24 (s, 1H), 8.09 (s,
1H), 8.01 (s, 1H), 7.97 (s, 1H), 7.90-7.85 (s, 2H), 7.76-7.74 (m, 1H), 7.71 (s, 1H), 7.68-
7.66 (m, 1H), 7.61-7.59 (m, 2H), 3.88 (s, 3H), 2.13 (s, 3H); LC-MS (ESI): Calculated
mass: 443.45; Observed mass: 444.1 [M+H]+ (RT: 1.3 min).
Example 151.
N-(2',6'-difluoro-5-(5-(l -methyl- lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
biphenyl-3-yl)acetamide
a)N-(2',6'-difluoro-5-nitrobiphenyl-3-yl)acetamide

A solution of N-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (20 g, 77
mmol) in 1,2-dimethoxyethane (250 ml) was degassed by N2 bubbling for 5 min. 2,6-
Difluorophenylboronic acid (14.6 g, 92.4 mmol, 1.2 eq.) was added and the mixture was
degassed for another 5 min. Pd(dppf)Cl2 (6.28 g, 7.7 mmol, 0.1 eq.) and aqueous
sodium carbonate (24.49 g, 231 mmol, 3.0 eq.) were added sequentially and the mixture
was further degassed for 5 min and then heated at 100 °C for 5 h. The reaction mixture
was quenched with water and extracted with ethyl acetate (3 x 200 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 30 % ethyl acetate in hexane) to give the title
product in 94 % yield (21.2 g). LC-MS (ESI): Calculated mass: 292.24; Observed mass:
293.1 [M+H]+(RT: 1.49 min).
b)N-(5-amino-2',6'-difluorobiphenyl-3-yl)acetamide
To a solution of N-(2',6'-difluoro-5-nitrobiphenyl-3-yl)acetamide (21 g, 72
mmol) in THF (200 ml) and methanol (50 ml) were added ammonium chloride (4.62 g,
86.4 mmol, 1.2 eq.) and zinc (5.44 g, 86.4 mmol, 1.2 eq.). The mixture was stirred at
room temperature for 6 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 95 % yield (18 g).
c)N-(5-(4-bromo-2-nitrophcnylamino)-2',6'-difluorobiphenyl-3-yl)acetamide
A solution of N-(5-amino-2',6'-difluorobiphenyl-3-yl)acetamide (8 g, 30.5
mmol), 4-bromo-l-fluoro-2-nitrobenzene (6.68 g, 30.5 mmol, 1.0 eq.) and potassium
fluoride (1.77 g, 30.5 mmol, 1.0 eq.) in DMF was heated at 130 °C for 5 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by

column chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to give the
title product in 96 % yield (13.5 g).
d)N-(5-(2-amino-4-bromophenylamino)-2',6'-difluorobiphenyl-3-yl)acetamide
To a solution of N-(5-(4-bromo-2-nitrophenylamino)-2',6'-difluorobiphenyl-3-
yl)acetamide (13.5 g, 29.22 mmol) in THF (200 ml) and methanol (25 ml) were added
ammonium chloride (12.51 g, 233.8 mmol, 8 eq.) and zinc (15.3 g, 233.8 mmol, 8 eq.).
The mixture was stirred at room temperature for 6 h and filtered. The filtrate was diluted
with water and extracted with ethyl acetate (3 x 100 ml). The combined organic layer
was washed with water, brine and dried over sodium sulphate. The solvent was distilled
off under reduced pressure to afford the title product in 95 % yield (12 g).
e)N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',6'-difluorobiphenyl-3-yl)-
acetamide
A mixture ofN-(5-(2-amino-4-bromophenylamino)-2',6'-difluorobiphenyl-3-yl)-
acetamide (12 g, 27.84 mmol) and formic acid (10 ml) was heated at 100 °C for 30 min.
The formic acid was distilled off under reduced pressure and the crude was dissolved in
ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 96 % yield (11.8 g).
f) N-(2',6'-difluoro-5-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-
biphenyl-3 -yl)acetamide
A solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',6'-difluorobiphenyl-
3-yl)acetamide (2.5 g, 5.67 mmol) in 1,2-dimethoxyethane (25 ml) was degassed by N2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-
zole (1.42 g, 6.8 mmol, 1.2 eq.) was added and the mixture was degassed for another 5
min. Pd(PPh3)4 (0.98 g, 0.85 mmol, 0.15 eq.) and aqueous sodium carbonate (1.2 g,
11.34 mmol, 2.0 eq.) were added sequentially and the mixture was further degassed for

5 min and then heated at 100 °C for 5 h. The reaction mixture was quenched with water
and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure and the residue was purified by column chromatography (60-120 silica
gel, 80 % ethyl acetate in hexane) to give the title product in 84 % yield (2.1 g). 1H
NMR (400 MHz, DMSO-d6): δ 10.39 (s, 1H), 8.56 (s, 1H), 8.18 (s, 1H), 8.05 (s, 1H),
7.97 (s, 1H), 7.92 (s, 1H), 7.71-7.47 (m, 5H), 7.27 (t, 2H), 3.85 (s, 3H), 2.09 (s, 3H);
LC-MS (ESI): Calculated mass: 443.45; Observed mass: 444.0 [M+H]+ (RT: 1.34 min).
Example 152.
N-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',6'-difluorobiphenyl-3-
yl)acetamide
To a solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-2',6'-difluorobi-
phenyl-3-yl)acetamide of Example 151(e) (2.5 g, 5.67 mmol) in DMF (20 ml) were
added pyrazole (0.96 g, 14.18 mmol, 2.5 eq.), copper(I) oxide (0.81 g, 5.67 mmol, 1 eq.)
and cesium carbonate (4.6 g, 14.18 mmol, 2.5 eq.) and the mixture was heated at 90 °C
for 48 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by preparative HPLC to give the title product in 91 % yield (2.2 g). *H
NMR (300 MHz, DMSO-ck): δ 10.43 (s, HI), 8.67 (s, 1H), 8.57 (d, 1H), 8.20 (d, HI),
8.06 (s, 1H), 7.92-7.88 (m, 1H), 7.77-7.74 (m, 3H), 7.53-7.49 (m, 2H), 7.30-7.25 (m,
2H), 6.54 (t, 1H), 2.1 (s, 3H); LC-MS (ESI): Calculated mass: 429.42; Observed mass:
430.1 [M+H]+ (RT: 1.50 min).
Example 153.
N-(3-(l-methyl-lH-pyrazol-4-yl)-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)phenyl)acetamide
a) N-(3-(l -methyl-lH-pyrazol-4-yl)-5-nitrophenyl)acetamide

A solution of AT-(3-bromo-5-nitrophenyl)acetamide (0.5 g, 1.9mmol) in 1,2-di-
methoxyethane (20 ml) was degassed by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-
tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.513 g, 2.47 mmol, 1.3 eq.) was
added and the mixture was degassed for another 5 min. Pd(dppf)Ci2 (0.155 g, 0.19
mmol, 0.1 eq.) and aqueous sodium carbonate (0.5 g, 4.75 mmol, 2.5 eq.) were added
sequentially and the mixture was further degassed for 5 min and then heated at 90 °C for
2 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3 x
50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (60-120 silica gel, 30 % ethyl acetate in
hexane) to give the title product in 81 % yield (0.4 g).
b) N-(3-amino-5-(l -methyl-1 H-pyrazol-4-yl)phenyl)acetamide
To a solution of N-(4'-methoxy-5-nitrobiphenyl-3-yl)acetamide (0.4 g, 1.54
mmol) in ethanol (25 ml) were added calcium chloride (0.34 g, 3.08 mmol, 2 eq.) and
iron powder (0.16 g, 3.08 mmol, 2 eq.) and the mixture was heated at 100 °C for 2 h and
filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 * 100
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure to afford the product in
85 % yield (0.3 g). LC-MS (ESI): Calculated mass: 230.27; Observed mass: 231.1
[M+H]+ (RT: 0.225 min).
c)N-(3-(4-bromo-2-nitrophenylamino)-5-(l-methyl-lH-pyrazol-4-yl)phenyl)-
acetamide
A solution of N-(3-amino-5-(l-methyl-lH-pyrazol-4-yl)phenyl)acetamide (0.3 g,
1.3 mmol), 4-bromo-l-fluoro-2-nitrobenzene (0.29 g, 1.3 mmol, 1.0 eq.) and potassium
fluoride (0.075 g, 1.3 mmol, 1.0 eq.) in DMF (5 ml) was heated at 100 °C for 12 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3*30 ml).
The combined organic layer was washed with water, brine and dried over sodium

sulphate. The solvent was distilled off under reduced pressure and the residue was
directly used for the next step.
d) N-(3-(2-amino-4-bromophenylamino)-5-(l -methyl- lH-pyrazol-4-yl)phenyl)-
acetamide
To a solution of N-(3-(4-bromo-2-nitrophenylamino)-5-(l-methyl-lH-pyrazol-4-
yl)phenyl)acetamide (0.6 g, 1.3 mmol) in ethanol (20 ml) were added calcium chloride
(0.29 g, 2.6 mmol, 2 eq.) and iron powder (0.14 g, 2.6 mmol, 2 eq.) and the mixture was
heated at 100 °C for 2 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 30 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was directly used for the next step.
e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(l-methyl-lH-pyrazol-4-yl)-
phenyl)acetamide
A mixture ofN-(3-(2-amino-4-bromophenylamino)-5-(l-methyl-lH-pyrazol-4-
yl)phenyl)acetamide (0.52 g, 1.3 mmol) and formic acid (2 ml) was heated at 100 °C for
30 min. The formic acid was distilled off under reduced pressure and the residue was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 54 % yield (0.28 g). LC-MS (ESI): Calculated mass: 410.27;
Observed mass: 411.0 [M+H]+ (RT: 0.84 min).
f) N-(3 -(1 -methyl-1 H-pyrazol-4-yl)-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1H-
benzo [d] imidazol-1 -yl)phenyl)acetamide
A solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(l-methyl-lH-p>Ta-
zol-4-yl)phenyl)acetamide (0.15 g, 0.365 mmol) in 1,2-dimethoxyethane (10 ml) was
degassed by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-
2-yl)-lH-pyrazole (0.091 g, 0.439 mmol, 1.2 eq.) was added and the mixture was

degassed for another 5 min. Pd(PPh3)4 (0.043 g, 0.037 mmol, 0.1 eq.) and aqueous
sodium carbonate (0.077 g, 0.73 mmol, 2.0 eq.) were added sequentially and the mixture
was further degassed for 5 min and then heated at 90 °C for 3 h. The reaction mixture
was quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by preparative
HPLC to give the title product in 12 % yield (18 mg). 1H NMR (300 MHz, CD3OD): δ
9.39 (s, 1H), 8.10-7.91 (m, 6H), 7.80-7.77 (m, 3H), 7.63 (s, 1H), 3.96 (s, 6H), 2.20 (s,
3H); LC-MS (ESI): Calculated mass: 443.45; Observed mass: 411.46 [M+Hf (RT: 0.28
min).
Example 154.
N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(2-oxopyri-
din-1 (2H)-yl)phenyl)acetamide
a) N-(3-nitro-5-(2-oxopyridin-1 (2H)-yl)phenyl)acetamide
To a solution of A^-bromo-S-nitropheny^acetamide (1 g, 3.85 mmol), pyridin-
2-ol (0.4 g, 4.24 mmol, 1.1 eq.), potassium carbonate (1 g, 1.3 mmol, 1.0 eq.) and
copper(I) iodide (10 mg) in toluene (20 ml) was added trans cyclohexyl diamine ( 5 mg,
0.039 mmol, 0.01 eq.) and the mixture was heated at 100 °C for 16 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 95 % yield (1 g).
b) N-(3-amino-5-(2-oxopyridin-l (2H)-yl)phenyl)acetamide
To a solution of N-(3-nitro-5-(2-oxopyridin-l(2H)-yl)phenyl)acetamide (1.2 g,
4.4 mmol) in ethanol (20 ml) and water (2 ml) were added calcium chloride (0.98 g, 8.8
mmol, 2 eq.) and iron powder (0.46 g, 8.8 mmol, 2 eq.) and the mixture was heated at

100 °C for 4 h and filtered. The filtrate was diluted with water and extracted with ethyl
acetate (3 x 100 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the product in 89 % yield (0.95 g). LC-MS (ESI): Calculated mass: 243.26;
Observed mass: 244.1 [M-rH]+ (RT: 0.19 min)
c)N-(3-(4-bromo-2-nitrophenylamino)-5-(2-oxopyridin-l(2H)-yl)phenyl)-
acetamide
A solution of N-(3-amino-5-(2-oxopyridin-l(2H)-yl)phenyl)acetamide (0.95 g,
3.9 mmol), 4-bromo-l-fluoro-2-nitrobenzene (0.86 g, 3.9 mmol, 1.0 eq.) and potassium
fluoride (0.23 g, 3.9 mmol, 1.0 eq.) in DMF (1 ml) was heated at 150 °C for 2 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (100-200 silica gel, 1 % methanol in DCM) to give
the title product in 69 % yield (1.2 g).
d)N-(3-(2-amino-4-bromophenylamino)-5-(2-oxopyTidin-l(2H)-yl)phenyl)acet-
amide
To a solution of N-(3-(4-bromo-2-nitrophenylamino)-5-(2-oxopyridin-l(2H)-yl)-
phenyl)acetamide (1.2 g, 2.7 mmol) in ethanol (20 ml) were added calcium chloride (0.6
g, 5.4 mmol, 2 eq.) and iron powder (0.28 g, 5.4 mmol, 2 eq.) and the mixture was
heated at 100 °C for 4 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the crude residue was directly used for the next step.
e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(2-oxopyridin-l(2H)-yl)phenyl)-
acetamide

A mixture of N-(3-(2-amino-4-bromophenylamino)-5-(2-oxopyridin-l(2H)-yl)-
phenyl)acetamide (1.12 g, 2.7 mmol) and formic acid (1 ml) was heated at 100°C for 2
h. The formic acid was distilled off under reduced pressure and the residue was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 61 % yield (0.7 g). LC-MS (ESI): Calculated mass: 423.26;
Observed mass: 424.9 [M+H]+ (RT: 1.065 min).
f) N-(3 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5 -(2-oxopyri-
din-1 (2H)-yl)phenyl)acetamide
A solution of N-(3-(5-bromo-1 H-benzo[d]imidazol-l -yl)-5-(2-oxopyridin-1 (2H)-
yl)phenyl)acetamide (0.7 g, 1.65 mmol) in 1,2-dimefhoxyethane (10 ml) was degassed
by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-
pyrazole (0.41 g, 1.98 mmol, 1.2 eq.) was added and the mixture was degassed for
another 5 min. Pd(PPli3)4 (0.19 g, 0.165 mmol, 0.1 eq.) and aqueous sodium carbonate
(0.35 g, 3.3 mmol, 2.0 eq.) were added sequentially and the mixture was further
degassed for 5 min and then heated at 90 °C for 4 h. The reaction mixture was quenched
with water and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 64 % yield (0.45 g). *H NMR (300 MHz, CD3OD-d6): δ 9.35 (s, 1H),
8.29-8.28 (m, 1H), 8.11 (s, 1H), 8.00 (s, 1H), 7.94 (d, 1H), 7.86-7.83 (m, 2H), 7.77-7.73
(m, 2H), 7.67-7.63 (m, 1H), 7.59 (t, 1H), 6.70-6.67 (m, 1H), 6.55 (dt, 1H), 3.96 (s, 3H),
2.20 (s, 3H); LC-MS (ESI): Calculated mass: 424.45; Observed mass: 425.2 [M+H]+
(RT: 0.23 min).
Example 155.
N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-5-( 1 H-l ,2,4-
triazol-1 -yl)phenyl)acetamide
a) N-(3-nitro-5-( 1H-1,2,4-triazol-1 -yl)phenyl)acetamide

To a solution of .V-Q-bromo-S-nitrophenyOacetamide (5 g. 19.3 mmol) in DMF
(50 ml) were added 1,2,4-triazole (3.3 g, 48.25 mmol, 2.5 eq.), copper(I) oxide (0.56 g,
3.86 mmol, 0.2 eq.) and cesium carbonate (12.5 g, 38.6 mmol, 2 eq.) and the mixture
was heated at 90 °C for 48 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3 * 100 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by column chromatography (60-120 silica gel, 30
% ethyl acetate in hexane) to give the title product in 86 % yield (4.1 g). LC-MS (ESI):
Calculated mass: 247.21; Observed mass: 248.0 [M+H]+ (RT: 0.257 min).
b)N-(3-amino-5-(lH-l,2,4-triazol-l-yl)phenyl)acetamide
To a solution of N-(3-nitro-5-(lH-l,2,4-triazol-l-yl)phenyl)acetamide (4.1 g,
16.6 mmol) in THF (50 ml) and methanol (10 ml) were added ammonium chloride (0.88
g, 16.6 mmol) and zinc (1.08 g, 16.6 mmol). The mixture was stirred at room
temperature overnight and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by column chromatography (60-120 silica gel, 3 %
methanol in DCM) to give the title product in 94 % yield (3.4 g).
c)N-(3-(4-bromo-2-nitrophenylamino)-5-(lH-l,2,4-triazol-l-yl)phenyl)acet-
amide
A solution of N-(3-amino-5-(lH-l,2,4-triazol-l-yl)phenyl)acetamide (3.43 g,
15.67 mmol), 4-bromo-l-fluoro-2-nitrobenzene (3.4 g, 15.67 mmol, 1.0 eq.) and
potassium fluoride (0.91 g, 15.67 mmol, 1.5 eq.) in DMF (5 ml) was heated at 80 °C for
7 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3 x
100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue

was purified by column chromatography (60-120 silica gel, 4 % methanol in DCM) to
give the title product in 80 % yield (5.2 g).
d)N-(3-(2-amino-4-bromophenylamino)-5-(lH-l,2,4-triazol-l-yl)phenyl)acet-
amide
To a solution of N-(3-(4-bromo-2-nitrophenylamino)-5-(lH-l,2,4-triazol-l-yl)-
phenyl)acetamide (5.2 g, 12.5 mmol) in ethanol (100 ml) were added calcium chloride
(2.78 g, 25 mmol, 2 eq.) and iron powder (1.3 g, 25 mmol, 2 eq.) and the mixture was
heated at 100 °C for 4 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 x 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the crude residue was directly used for the next step.
e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-l,2,4-triazol-l-yl)phenyl)-
acetamide
A mixture ofN-(3-(2-amino-4-bromophenylamino)-5-(lH-l,2,4-triazol-l-yl)-
phenyl)acetamide (4.84 g, 12.5 mmol) and formic acid (10 ml) was heated at 80 °C for 2
h. The formic acid was distilled off under reduced pressure and the residue was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 85 % yield (4.2 g).
f) N-(3-(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1H-1,2,4-
triazol-1 -yl)phenyl)acetamide
A solution of N-(3-(5-bromo-1 H-benzo[d]imidazol-1 -yl)-5-( 1H-1,2,4-triazol-1 -
yl)phenyl)acetamide (100 mg, 0.25 mmol) in 1,2-dimethoxyethane (10 ml) was
degassed by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-
2-yl)-lH-pyrazole (62 mg, 0.3 mmol, 1.2 eq.) was added and the mixture was degassed
for another 5 min. Pd(PPh3)4 (35 mg, 0.03 mmol, 0.12 eq.) and aqueous sodium

carbonate (0.53 g, 0.5 mmol, 2.0 eq.) were added sequentially and the mixture was
further degassed for 5 min and then heated at 90 °C for 4 h. The mixture was quenched
with water and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 50 % yield (50 mg). 1H NMR (400 MHz, DMSO-d6): δ 10.50 (s, 1H),
9.36 (s, 1H), 8.77 (s, 1H), 8.28 (s, 1H), 8.19-8.18 (m, 2H), 8.00-7.93 (m, 4H), 7.72 (d,
1H), 7.60 (dd, 1 H), 3.86 (s, 3H), 2.11 (s, 3H); LC-MS (ESI): Calculated mass: 398.42;
Observed mass: 399.4 [M+H]+ (RT: 0.13 min).
Example 156.
N-(3 -(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-(fhiazol-2-
yl)phenyl)acetamide
a)N-(3-nitro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide
A solution of N-(3-bromo-5-nitrophenyl)acetamide (2.1 g, 8.1 mmol) in 1,2-di-
methoxyethane (25 ml) was degassed by N2 bubbling for 5 min. Bis(pinacolato)diboron
(3.09 g, 12.15 mmol, 1.3 eq.) was added and the mixture was degassed for another 5
min. Pd(dppf)Cl2 (0.066 g, 0.081 mmol, 0.1 eq.) and potassium acetate (2.38 g, 24.3
mmol, 3 eq.) were added sequentially and the mixture was further degassed for 5 min
and then heated at 90 °C for a period of 2 h. The reaction mixture was quenched with
water and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by column chromatography (60-120
silica gel, 30 % ethyl acetate in hexane) to give the title product in 60 % yield (1.5 g).
b)N-(3-nitro-5-(thiazol-2-yl)phenyl)acetamide
A solution of N-(3-nitro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)-
acetamide (2.8 g, 9.14 mmol) in 1,2-dimethoxyethane (10 ml) was degassed by N2
bubbling for 5 min. 2-Bromothiazole (1 g, 9.14 mmol, 1 eq.) was added and the mixture

was degassed for another 5 min. Pd(dppf)Cl2 (0.74 g, 0.91 mmol, 0.1 eq.) and aqueous
sodium carbonate (1.9 g, 18.2 mmol, 2 eq.) were added sequentially and the mixture was
further degassed for 5 min and then heated at 80 °C for 2 h. The mixture was quenched
with water and extracted with ethyl acetate (3 * 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by column chromatography (60-120
silica gel, 40 % ethyl acetate in hexane) to give the title product in 33 % yield (0.8 g). *H
NMR (300 MHz, DMSO-de): § 10.64 (s, 1H), 8.65 (t, 1H), 8.55 (t, 1H), 8.34 (t, 1H),
8.04 (d, 1H), 7.94 (d, 1H), 2.13 (s, 3H).
c)N-(3-amino-5-(thiazol-2-yl)phenyl)acetamide
To a solution of N-(3-nitro-5-(thiazol-2-yl)phenyl)acetamide (0.8 g, 3.03 mmol)
in methanol (25 ml) and ethyl acetate (10 ml) was added 10 % Pd/C (300 mg, 0.1 eq.)
and the reaction vessel was purged with nitrogen gas for 5 min. The mixture was then
hydrogenated with H2 balloon for 12 h. The mixture was filtered through a pad of celite
and the filtrate was concentrated under reduced pressure to afford the title compound in
71 % yield (0.5 g). 1H NMR (300 MHz, DMSO-d6): δ 9.83 (s, 1H), 7.86-7.85 (m, 1H),
7.71-7.70 (m, 1H), 7.35 (s, 1H), 7.04 (s, 1H), 6.88 (s, 1H), 5.45 (br s, 2H), 2.03 (s, 3H).
d)N-(3-(4-bromo-2-nitrophenylamino)-5-(thiazol-2-yl)phenyl)acetamide
A solution of N-(3-amino-5-(fhiazol-2-yl)phenyl)acetamide (0.5 g, 2.14 mmol),
4-bromo-l-fluoro-2-nitrobenzene (0.47 g, 2.14 mmol, 1.0 eq.) and potassium fluoride
(0.19 g, 3.21 mmol, 1.5 eq.) in DMF was heated at 80 °C for 7 h. The reaction mixture
was quenched with water and extracted with ethyl acetate (3 x 100 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to give the title
product in 24 % yield (0.22 g).
e)N-(3-(2-amino-4-bromophenylamino)-5-(thiazol-2-yl)phenyl)acetamide

To a solution of N-(3-(4-bromo-2-nitrophenylamino)-5-(thiazol-2-yl)phenyl)-
acetamide (0.22 g, 0.507 mmol) in THF (15 ml) were added a solution of ammonium
chloride (0.11 g, 2.02 mmol, 4 eq.) in water (5 ml) and zinc (0.13 g, 2.02 mmol, 4 eq.).
The mixture was stirred at room temperature overnight and filtered. The filtrate was
diluted with water and extracted with ethyl acetate (3 x 100 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure to afford the title product in 83 % yield (0.17 g).
f) N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(thiazol-2-yl)phenyl)acetamide
A mixture of N-(3-(2-amino-4-bromophenylamino)-5-(thiazol-2-yl)phenyl)acet-
amide (0.17 g. 0.42 mmol) and formic acid (3 ml) was heated at 80 °C for 2 h. The
formic acid was distilled off under reduced pressure and the crude was dissolved in
ethyl acetate. The ethyl acetate layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 86 % yield (0.15 g).1HNMR (300 MHz, DMSO-d6): δ 10.52 (s, 1H), 8.77 (s,
1H), 8.32 (s, 1H), 8.07-8.00 (m, 3H), 7.90-7.87 (m, 2H), 7.66-7.63 (m, 1H), 7.55 (s,
lH),2.13(s,3H).
g)N-(3-(5-(l-methyl-lH-p>Tazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(thiazol-2-
yl)phenyl)acetamide
A solution of A^-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(thiazol-2-yl)phenyl)-
acetamide (0.2 g, 0.48 mmol) in 1,2-dimethoxyethane (15 ml) was degassed byN2
bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyra-
zole (0.15 g, 0.73 mmol, 1.5 eq.) was added and the mixture was degassed for another 5
min. Pd(PPh3)4 (0.11 g, 0.096 mmol, 0.2 eq.) and aqueous sodium carbonate (0.1 g, 0.96
mmol, 2.0 eq.) were added sequentially and the mixture was further degassed for 5 min
and then heated at 110 °C for a period of 3 h. The mixture was quenched with water and
extracted with ethyl acetate (3 * 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced

pressure and the residue was purified by preparative HPLC to give the title product in
1.5 % yield (3 mg). 1H NMR (300 MHz, CD3OD): 6 8.20-8.1 l(m, 2H), 8.05-7.82 (m,
5H), 7.68-7.61 (m, 3H), 7.55-7.45 (m, 1H), 3.88 (s, 3H), 2.12 (s, 3H); LC-MS (ESI):
Calculated mass: 414.48; Observed mass: 415.0 [M+H]+ (RT: 0.31 min).
Example 157.
N-(3-(lH-indol-3-yl)-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-
yl)phenyl)acetamide
a)N-(3-nitro-5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acetamide
A solution of A-(3-bromo-5-nitrophenyl)acetamide (0.38 g, 1.48 mmol) in 1,2-
dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. l-(Phenylsulfonyl)-3-
(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-indole (0.68 g, 1.77 mmol, 1.2 eq.)
was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.12 g, 0.148
mmol, 0.1 eq.) and aqueous sodium carbonate (0.47 g, 4.45 mmol, 3.0 eq.) were added
sequentially and the mixture was further degassed for 5 min and then heated at 100 °C
for 2 h. The mixture was quenched with water and extracted with ethyl acetate (3 x 50
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 30 % ethyl acetate in hexane) to
give the title product in 77 % yield (0.5 g).
b)N-(3-amino-5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acetamide
To a solution of Af-(3-nitro-5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acet-
amide (1 g, 2.29 mmol) in methanol (10 ml) was added 10 % PdVC (100 mg, 0.1 eq.)
and the reaction vessel was purged with nitrogen gas for 5 min. The mixture was then
hydrogenated with H2 balloon for 12 h. The mixture was filtered through a pad of celite
and the filtrate was concentrated under reduced pressure to afford the title compound in
89 % yield (0.83 g).

c)N-(3-(4-bromo-2-nitrophenylamino)-5-(l-(phenylsulfonyl)-lH-indol-3-yl)-
phenyl)acetamide
A solution of N-(3-amino-5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acetamide
(0.83 g, 2.04 mmol), 4-bromo-l-fluoro-2-nitrobenzene (0.45 g, 2.04 mmol, 1.0 eq.) and
potassium fluoride (0.12 g, 2.04 mmol, 1.0 eq.) in DMF (10 ml) was heated at 130 °C
for 5 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (60-120 silica gel, 30 % ethyl acetate in
hexane) to give the title product in 48 % yield (0.6 g).
d)N-(3-(2-amino-4-bromophenylamino)-5-(l-(phenylsulfonyl)-lH-indol-3-yl)-
phenyl)acetamide
To a solution of N-(3-amino-5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acet-
amide (0.61 g, 1 mmol) in THF (10 ml) and methanol (10 ml) were added a solution of
ammonium chloride (0.53 g, 10 mmol, 10 eq.) in water (5 ml) and zinc (0.63 g, 10
mmol, 10 eq.). The mixture was stirred at room temperature for 6 h and filtered. The
filtrate was diluted with water and extracted with ethyl acetate (3 * 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure to give the title product in 70 %
yield (0.4 g).
e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(l-(phenylsulfonyl)-lH-indol-3-
yl)phenyl)acetamide
A mixture of N-Q -(2-amino-4-bromophenylamino)-5-( 1 -(phenylsulfonyl)-1H-
indol-3-yl)phenyl)acetamide (0.4 g, 0.7 mmol) and formic acid (10 ml) was heated at
100 °C for 30 min. The formic acid was distilled off under reduced pressure and the
crude was dissolved in ethyl acetate. The ethyl acetate layer was washed with water,

brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 73 % yield (0.3 g).
f)N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(l-(phenyl-
sulfonyl)-1 H-indol-3 -yl)phenyl)acetamide
A solution of N-(3-(5-bromo-1 H-benzo[d]imidazol-1 -yl)-5-( 1 -(phenylsulfonyl)-
1 H-indol-3-yl)phenyl)acetamide (0.3 g, 0.5 mmol) in 1,2-dimethoxyethane (15 ml) was
degassed by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,54etramefhyl-l,3,2-dioxaborolan-
2-yl)-lH-pyrazole (0.13 g, 0.62 mmol, 1.2 eq.) was added and the mixture was degassed
for another 5 min. Pd(PPh;,)4 (0.057 g, 0.05 mmol, 0.1 eq.) and aqueous sodium
carbonate (0.16 g, 1.54 mmol, 3.0 eq.) were added sequentially and the mixture was
further degassed for 5 min and then heated at 90 °C for 3 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined organic
layer was washed with water, brine and dried over sodium sulphate. The solvent was
distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the title
product in 100 % yield (0.29 g). LC-MS (ESI): Calculated mass: δ86.66; Observed
mass: δ87.2 [M+H]+ (RT: 1.53 min).
g) N-(3-(1 H-indol-3-yl)-5-(5-( 1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-
1 -yl)phenyl)acetamide
To a solution of N-(3-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
5-(l-(phenylsulfonyl)-lH-indol-3-yl)phenyl)acetamide (0.3 g, 0.5 mmol, 1 eq.) in THF
(10 ml) and methanol (10 ml) was added cesium carbonate (0.33 g, 1 mmol, 2 eq.) and
the mixture was stirred at room temperature for 12 h. The reaction mixture was
quenched with water and extracted with ethyl acetate (3 x 100 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure to afford the title product in 7 % yield (15 mg).
1H NMR (400 MHz, DMSO-d6): δ 11.52 (s, 1H), 10.33 (s, 1H), 8.65 (s, 1H), 8.19 (s,
1H), 8.04-7.89 (m, 4H), 7.68 (d, 1H), 7.60-7.58 (m, 2H), 7.49-7.47 (m, 3H), 7.21-7.13

(m, 211), 3.88 (s, 311), 2.13 (s, 311); LC-MS (ESI): Calculated mass: 446.50; Observed
mass: 447.1 [M+H]+ (RT: 0.55 min).
Example 158.
N-(3-(6-methoxypyridin-3 -yl)-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d]-
imidazol-1 -yl)phenyl)acetamide
a)N-(3-(6-methoxypyridin-3-yl)-5-nitrophenyl)acetamide
A solution of N-(3-bromo-5-nitrophenyl)acetamide (1 g, 3.86 mmol) in 1,2-di-
methoxyethane (20 ml) was degassed by N2 bubbling for 5 min. (6-Methoxypyridin-3-
yl)boronic acid (0.77 g, 5.0 mmol, 1.3 eq.) was added and the mixture was degassed for
5 min. Pd(dppf)Cl2 (0.630 g, 0.77 mmol, 0.2 eq.) and aqueous sodium carbonate (1.23 g,
11.58 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for
5 min and then heated at 90 °C for 2 h. The mixture was quenched with water and
extracted with ethyl acetate (3 * 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by column chromatography (60-120 silica gel, 40
% ethyl acetate in hexane) to give the the title product in 81 % yield (0.9 g).
b)N-(3-amino-5-(6-methoxypyridin-3-yl)phenyl)acetamide
To a solution of N-(3-(6-methoxypyridin-3-yl)-5-nitrophenyl)acetamide (0.9 g,
3.13 mmol) in methanol (50 ml) was added 10 % Pd/C (250 mg) and the reaction vessel
was purged with nitrogen gas for 5 min. The mixture was then hydrogenated with H?
balloon for a period of 4 h. The mixture was filtered through a pad of celite and the
filtrate was concentrated under reduced pressure to afford the title compound in 99 %
yield (0.8 g).
c)N-(3-((4-bromo-2-nitrophenyl)amino)-5-(6-methoxypyridin-3-yl)phenyl)acet-
amide

A solution of N-(3-amino-5-(6-methoxypyridin-3-yl)phenyl)acetamide (0.8 g,
3.11 mmol), 4-bromo-l-fluoro-2-nitrobenzene (0.68 g, 3.11 mmol, 1.0 eq.) and
potassium fluoride (0.18 g, 3.111 mmol, 1.0 eq.) in DMF (5 ml) was heated at 90 °C for
20 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3
x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in
hexane) to give the title product in 42 % yield (0.6 g). LC-MS (ESI): Calculated mass:
457.28; Observed mass: 458.9 [M+H]+ (RT: 1.71 min).
d)N-(3-((2-amino-4-bromophenyl)amino)-5-(6-methoxyp>Tidin-3-yl)phenyl)-
acetamide
To a solution of N-(3-((4-bromo-2-nitrophenyl)amino)-5-(6-methoxypyridin-3-
yl)phenyl)acetamide (0.3 g, 0.66 mmol) in ethanol (20 ml) and water (5 ml) were added
calcium chloride (0.73 g, 6.6 mmol, 10 eq.) and iron powder (0.36 g, 6.6 mmol, 10 eq.)
and the mixture was heated at 90 °C for 6 h and filtered. The filtrate was diluted with
water and extracted with ethyl acetate (3 x 100 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the crude residue was directly used for the next step.
e)N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(6-methoxypyridin-3-yl)phenyl)-
acetamide
A mixture ofN-(3-((2-amino-4-bromophenyl)amino)-5-(6-methoxypyridin-3-
yl)phenyl)acetamide (0.26 g, 0.61 mmol) and formic acid (5 ml) wras heated at 100 °C
for 2 h. The formic acid was distilled off under reduced pressure and the crude was
dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure and the
residue was purified by column chromatography (60-120 silica gel, 10 % methanol in
chloroform) to give the title product in 86 % yield (0.23 g). LC-MS (ESI): Calculated
mass: 437.29; Observed mass: 438.0 [M+H]+ (RT: 1.52 min).

f)N-(3-(6-methoxypyridin-3-yl)-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)phenyl)acetamide
A solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(6-methoxypyridin-3-
yl)phenyl)acetamide (0.22 g, 0.5 mmol) in 1,2-dimethoxyethane (20 ml) was degassed
by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-
pyrazole (0.11 g, 0.55 mmol, 1.1 eq.) was added and the mixture was degassed for
another 5 min. Pd(PPh3)4 (0.116 g, 0.1 mmol, 0.2 eq.) and aqueous sodium carbonate
(0.16 g, 1.5 mmol, 3.0 eq.) were added sequentially and the mixture was further
degassed for 5 min and then heated at 90 °C for 3 h. The mixture was quenched with
wrater and extracted with ethyl acetate (3 x 50 ml). The combined organic layer was
washed with water, brine and dried over sodium sulphate. The solvent was distilled off
under reduced pressure and the residue was purified by preparative HPLC to give the
title product in 18 % yield (40 mg). *H NMR (300 MHz, DMSO-d6): δ 10.4 (s, 1H),
8.82 (s, 1H), 8.55 (s, 1H), 8.23 (s, 1H), 8.1-8.04 (m, 2H), 7.98-7.91 (m, 2H), 7.85 (s,
1H), 7.74-7.65 (m, 3H), 6.97 (d, 1H), 3.92 (s, 3H), 3.88 (s, 3H), 2.12 (s, 3H); LC-MS
(ESI): Calculated mass: 438.48; Observed mass: 439.1 [M+H]+ (RT: 0.4 min).
Example 159.
N-(5-(5-( 1 H-pyrazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-2',4'-difluoro-[l, 1 '-bi-
phenyl] -3 -yl)propionamide
To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fiuorobiphenyl-3-amine of Example 29(a) (0.5 g, 1.3 mmol) in DMF (10 ml) was added
2-( 1 H-7-azabenzotriazol-1 -yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate
methanaminium (HATU) (0.98 g, 2.6 mmol, 2.0 eq.) followed by DIPEA (0.5 g, 3.9
mmol, 3 eq.) and propionic acid (0.19 g, 2.6 mmol, 2.0 eq.). The mixture was stirred for
4 h, quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by preparative
HPLC to give the title product in 9 % yield (50 mg). ]H NMR (300 MHz, DMSO-d6): δ

10.12 (s, 1H), 8.9-8.8 (s, 1H ), 8.6 (d, 1H), 8.2 (s, 1H), 8.12 (s, 1H), 7.95 (d, 1H), 7.89-
7.82 (m, 2H), 7.8-7.7 (m, 2H), 7.55 (s, 1H), 7.45-7.40 (m, 1H), 7.3-7.22 (m, 1H), 6.6-
6.52 (s, 1H), 2.4 (quartet, 2H), 1.15 (t, 3H); LC-MS (ESI): Calculated mass: 443.45;
Observed mass: 444.1 [M+H]+ (RT: 1.58 min).
Example 160.
N^S^S^lH-pyrazol-l-yO-lH-benzofdJimidazol-l-yl^'^'-difluoro-tl,!'-
biphenyl]-3-yl)isobutyramide
The compound was prepared from the compound of Example 29(a) using the
procedures described in Example 159. *H NMR (300 MHz, DMSO-d6): δ 10.28 (s, 1H),
8.8 (s, 1H), 8.58 (d, 1H), 8.22 (d, 1H), 8.11 (s, 1H), 7.95 (d, 1H), 7.92 (d, 1H), 7.87 (d,
1H), 7.82 (s, 1H), 7.78 (s, 1H), 7.53 (s, 1H), 7.45 (d, 1H), 7.25 (s, 1H), 6.55-6.54 (m,
1H), 2.67-2.58 (m, 1H), 1.12 (d, 6H); LC-MS (ESI): Calculated mass: 457.47; Observed
mass: 458.1 [M+H]+ (RT: 1.6 min).
Example 161.
N-(5-(5-(l H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',4'-difluoro-[ 1,1 '-bi-
phenyl] -3 -y l)cyclopropanecarboxamide
The compound was prepared from the compound of Example 29(a) using the
procedures described in Example 159. 1H NMR (300 MHz, DMSO-d6): δ 10.63 (s, 1H),
8.72 (s, 1H), 8.57 (d, 1H), 8.21 (d, 1H), 8.08 (s, 1H), 7.93-7.74 (m, 5H), 7.52 (s, 1H),
7.46-7.39 (m, 1H), 7.29-7.23 (m, 1H), 6.55 (s, 1H), 1.85-1.79 (m, 1H), 0.87 (d, 4H);
LC-MS (ESI): Calculated mass: 455.46; Observed mass: 456.1 [M+H]+ (RT: 1.58 min).
Example 162.
N-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-difluoro-[l,r-bi-
phenyl]-3 -yl)pivalamide
The compound was prepared from the compound of Example 29(a) using the
procedures described in Example 159. 1H NMR (400 MHz, DMSO-d6): δ 9.65 (s, 1H),
8.74 (s, 1H), 8.0 (d, 1H), 8.23 (d, 1H), 8.17 (s, 1H), 8.01 (s, 1H), 7.95-7.92 (m, 1H),

7.84-7.81 (m, 1H), 7.78-7.72 (m, 2H), 7.54 (s, 1H), 7.48-7.42 (m, 1H), 7.29-7.25 (m,
1H), 6.57-6.56 (m, 1H), 1.27 (s, 9H); LC-MS (ESI): Calculated mass: 471.5; Observed
mass: 472.2 [M+H]+ (RT: 1.68 min).
Example 163.
N-(5-(5 -(1 H-pyrazol-1 -yl)-1 H-benzo[d] imidazol-1 -yl)-2',4'-difluoro- [ 1,1 '-bi-
phenyl]-3-yl)-2-morpholinoacetamide
To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-di-
fluorobiphenyl-3-amine of Example 29(a) (0.1 g, 0.26 mmol) in DMF (3 ml) was added
EDC (74 mg, 0.39 mmol, 1.5 eq.), HOBt (70 mg, 0.52 mmol, 2 eq.) followed by DIPEA
(0.1 g, 0.77 mmol, 3 eq.) and 2-morpholinoacetic acid (Intermediate Example 10) (56
mg, 0.39 mmol, 1.5 eq.). The mixture was stirred for 12 h, quenched with water and
extracted with ethyl acetate (3 * 50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the crude residue was purified by preparative HPLC to give the title
product in 27 % yield (36 mg). 1H NMR (400 MHz, D20): δ 8.74 (s, 1H), 8.60 (d, 1H),
8.24 (d, 1H), 8.14 (s, 1H), 7.96-7.91 (m, 2H), 7.84-7.76 (m, 3H), 7.57 (s, lH),7.49-7.40
(m, 1H), 7.35-7.22 (m, 1H), 6.56 (m, 1H), 3.66 (t, 4H), 3.61-3.59 (m, 4H), 3.21 (s, 2H);
LC-MS (ESI): Calculated mass: δ14.53; Observed mass: δ15.1 [M+H]+ (RT: 0.53 min).
Example 164.
N-(2,,4'-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)-[ 1,1 '-biphenyl] -3 -yl)acetamide
A mixture ofN-(5-(5-ethynyl-lH-benzo[d]imidazol-l-yl)-2',4'-difluorobiphenyl-
3-yl)acetamide of Example 17(e) (0.7 g, 1.8 mmol), 4-azido-l-methylpiperidine (0.3 g,
2.17 mmol, 1.2 eq.), sodium ascorbate (0.35 g, 1.8 mmol, 1.0 eq.) and copper sulfate
pentahydrate (0.22 g, 0.9 mmol, 0.5 eq.) in DMSO, DCM and water (1:1:1, 3 ml) was
stirred for 12 h at room temperature. The reaction mixture was quenched with water and
the precipitate formed was filtered and dried to give the crude product which was
recrystallized from diethyl ether to give the title product in 71 % yield (0.67 g). [H NMR

(300 MHz, DMSO-d6): δ 10.41 (s, 1H), 8.75 (s, 2H), 8.28 (d, 1H), 8.11 (s, 1H), 7.95-
7.92 (m, 1H), 7.81-7.74 (m, 2H), 7.53 (s, 1H), 7.45 (m, 1H), 7.27 (m, 1H), 3.66-3.62 (m,
1H), 3.26-3.22 (m, 4H), 2.87 (s, 3H), 2.27-2.22 (m, 4H), 2.12 (m, 3H); LC-MS (ESI):
Calculated mass: δ27.57; Observed mass: δ28.2 [M+H]+ (RT: 0.19 min).
Example 165.
N-(2',4'-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)- [ 1,1 '-biphenyl] -3 -yl)ethanesulfonamide
a) 2',4'-difluoro-5-(5-( 1 -(1 -methylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1H-
benzo [d] imidazol-1 -yl) - [ 1,1 '-biphenyl] -3 -amine
A solution of N-(2',4'-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-
4-yl)-lH-benzo[d]imidazol-l-yl)-[l,l'-biphenyl]-3-yl)acetamide of Example 164 (0.48
g, 0.91 mmol) in 6 N HC1 (10 ml) was heated at 70 °C for 3 h. The reaction mixture was
quenched with NaHCC>3 solution and extracted with ethyl acetate (3 * 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure to afford the title product in 27 %
yield (0.12 g).
b)N-(2',4'-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-1,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)- [ 1,1 '-biphenyl] -3-yl)ethanesulfonamide
To a solution of 2,,4'-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-
4-yl)-lH-benzo[d]imidazol-l-yl)-[l,l'-biphenyl]-3-amine (60 mg, 0.123 mmol) in DCM
(2 ml) was added pyridine (19 mg, 0.246 mmol, 2.0 eq.) followed by ethanesulfonyl
chloride (19 mg, 0.148 mmol, 1.2 eq.). The reaction was monitored by LCMS. After
completion of the reaction the solvent was removed under reduced pressure and the
crude product was purified by flash chromatography (using 2 % methanol in
chloroform) to give the title product in 13 % yield (9 mg). LC-MS (ESI): Calculated
mass: δ77.65; Observed mass: δ78.2 [M+H]+ (RT: 0.42 min).

Example 166.
N-(2',4,-difluoro-5-(5-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-lH-
benzo [d] imidazol-1 -yl)- [1,1 '-biphenyl] -3-yl)cyclopropanesulfonamide
The compound was prepared from the compound of Example 164 using the
procedures described in Example 165. LC-MS (ESI): Calculated mass: δ53.61;
Observed mass: δ54.2 [M+H]~ (RT: 0.57 min).
Example 167.
N-(2',4'-difluoro-5-(5-(l-isopropyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
[ 1, l'-biphenyl]-3-yl)acetamide
The compound was prepared from compound of Intermediate Example 12 using
the procedure described in Example 8. 1H NMR (300 MHz, DMSO-d6): δ 10.43 (s, 1H),
9.12 (s, 1H), 8.34 (s, 1H), 8.12 (s, 1H), 8.02-7.97 (m, 2H), 7.81 (s, 1H), 7.75-7.67 (m,
3H), 7.55 (s, 1H), 7.47-7.41 (m, 1H), 7.29-7.22 (m, 1H), 4.52-4.45 (m, 1H), 2.10 (s,
3H), 1.45 (d, 6H); LC-MS (ESI): Calculated mass: 471.5; Observed mass: 471.6
[M+Hf (RT: 1.4 min).
Example 168.
N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-3-yl)-lH-benzo[d]imidazol-l-yl)-
[1,1 '-biphenyl]-3 -yl)acetamide
a)N-(5-((4-acetyl-2-nitrophenyl)amino)-2')4'-difluoro-[l,T-biphenyl]-3-yl)acet-
amide
A solution of N-(5-amino-2',4'-difluorobiphenyl-3-yl)acetamide of Example 1(e)
(0.6 g, 2.28 mmol), l-(4-fluoro-3-nitrophenyl)ethanone (0.4 g, 2.28 mmol, 1.0 eq.) and
potassium fluoride (0.26 g, 4.56 mmol, 2.0 eq.) in DMF was heated at 80 °C for 7 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 * 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was

purified by column chromatography (60-120 silica gel, 1 % methanol in chloroform) to
give the title product in 68 % yield (0.66 g). *H NMR (300 MHz, DMSO-cfc): δ 10.18 (s,
1H), 9.83 (s, 1H), 8.63 (d, 1H), 8.01 (m, 1H), 7.71 (s, 1H), 7.59 (m, 2H), 7.35 (m, 1H),
7.27-7.16 (m, 3H), 2.52 (s, 3H), 2.05 (s, 3H).
b) (E)-N-(5-((4-(3-(dimethylamino)acryloyl)-2-nitrophenyl)amino)-2',4'-difluoro-
[1,1 '-biphenyl]-3-yl)acetamide
To a solution of N-(5-((4-acetyl-2-nitrophenyl)amino)-2',4'-difluoro-[l,r-
biphenyl]-3-yl)acetamide (0.66 g, 1.55 mmol) in DMF (4 ml) and ethanol (4 ml) was
added DMF dimethylacetal (7 ml) and stirred at 110 °C for 12 h. The mixture was
extracted with ethyl acetate (3 x 50 ml) and the combined organic layer was washed
with water, brine and dried over sodium sulphate. The solvent was distilled off under
reduced pressure to give the product in 89 % yield (0.66 g) which was directly used for
the next step.
c)N-(2',4'-difluoro-5-((4-(l-methyl-lH-pyrazol-3-yl)-2-nitrophenyl)amino)-[ 1,1'-
biphenyl] -3 -yl)acetamide
To a solution of (E)-N-(5-((4-(3-(dimethylamino)acryloyl)-2-nitrophenyl)amino)-
2',4'-difluoro-[l,r-biphenyl]-3-yl)acetamide (0.66 g, 1.37 mmol) in ethanol (15 ml) was
added methyl hydrazine (7 ml) and stirred at room temperature overnight. The reaction
mixture was quenched with chilled water and the solid formed was filtered, washed with
water and used for the next step. 1H NMR (300 MHz, DMSO-de): δ 10.12 (s, 1H), 9.52
(s, 1H), 8.19 (d, 1H), 7.73-7.60 (m, 2H), 7.59-7.54 (m, 2H), 7.46-7.35 (m, 3H), 7.30-
7.14 (m, 2H), 6.44 (d, 1H), 3.85 (s, 3H), 2.05 (s, 3H).
d) N-(5-((2-amino-4-(l-methyl-lH-pyrazol-3-yl)phenyl)amino)-2',4'-difluoro-
[1,1 '-biphenyl]-3-yl)acetamide
To a solution of N-(2',4'-difluoro-5-((4-(l-methyl-lH-pyrazol-3-yl)-2-nitro-
phenyl)amino)-[l,l'-biphenyl]-3-yl)acetamide (0.5 g, 1.07 mmol) in THF (20 ml) were

added a solution of ammonium chloride (0.23 g, 4.28 mmol, 4 eq.) in water (10 ml) and
zinc (0.28 g, 4.28 mmol, 4 eq.). The mixture was stirred at room temperature for 4 h and
filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 x 100
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure to afford the title product
in 65 % yield (0.3 g). LC-MS (ESI): Calculated mass: 433.45; Observed mass: 434.1
[M+H]+ (RT: 0.49 min).
e)N-(2',4'-difluoro-5-(5-(l-methyl-lH-pyrazol-3-yl)-lH-benzo[d]imidazol-l-yl)-
[1 ,l'-biphenyl]-3-yl)acetamide
A mixture of N-(5-(2-amino-4-bromophenylamino)-2\4'-difluorobiphenyl-3-
yl)acetamide (0.3 g, 0.69 mmol) and formic acid (3 ml) was heated at 100 °C for 2 h.
The formic acid was distilled off under reduced pressure and the crude was extracted
with in ethyl acetate. The solvent was distilled off under reduced pressure and the
residue was purified by preparative HPLC to give the title product in 9 % yield (28 mg).
]H NMR (300 MHz, DMSO-d6): δ 10.42 (s, 1H), 8.81 (s, 1H), 8.10 (s, 1H), 7.96 (s,
1H), 7.83-7.72 (m, 3H), 7.54-7.42 (m, 4H), 7.30-7.25 (m, 1H), 6.45 (d, 1H), 3.9 (s, 3H),
2.13 (s, 3H); LC-MS (ESI): Calculated mass: 443.45; Observed mass: 443.7 [M+H]+
(RT: 1.37 min).
Example 169.
N-(5-(5-(4,5-dihydro-lH-imidazol-2-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-
difluoro-[l,l'-biphenyl]-3-yl)acetamide
a)N-(5-((4-(4,5-dihydro-lH-imidazol-2-yl)-2-nitrophenyl)amino)-2,,4'-difluoro-
[1,1 '-biphenyl] -3 -yl)acetamide
To a solution of N-(2',4'-difluoro-5-(4-formyl-2-nitrophenylamino)biphenyl-3-
yl)acetamide of Example 22(a) (200 mg, 0.49 mmol) in DCM (10 ml) at 0 °C was added
ethylene diamine (0.036 ml, 0.54 mmol, 1.1 eq.) followed by N-bromosuccinimide (95
mg, 0.54 mmol, 1.1 eq.). The mixture was stirred for 12 h, quenched with water and

extracted with DCM (3x50 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified column chromatography (60-120 silica gel, 20 %
methanol in chloroform) to give the title product in 50 % yield (0.11 g). LC-MS (ESI):
Calculated mass: 451.43; Observed mass: 452.1 [M+H]+ (RT: 0.63 min).
b)N-(5-((2-amino-4-(4,5-dihydro-lH-imidazol-2-yl)phenyl)amino)-2',4'-
difluoro-[ 1,1 '-biphenyl]-3-yl)acetamide
To a solution of N-(5-((4-(4,5-dihydro-lH-imidazol-2-yl)-2-nitrophenyl)amino)-
2,,4'-difluoro-[l,l'-biphenyl]-3-yl)acetamide (0.11 g, 0.23 mmol) in THF (10 ml) were
added a solution of ammonium chloride (50 mg, 0.93 mmol, 4 eq.) in water (10 ml) and
zinc (60 mg, 0.93 mmol, 4 eq.). The mixture was stirred at room temperature for 4 h and
filtered. The filtrate was diluted with water and extracted with ethyl acetate (3 * 100
ml). The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure to afford the title product
in 88 % yield (85 mg). LC-MS (ESI): Calculated mass: 421.44; Observed mass: 422.2
[M+H]+ (RT: 0.49 min).
c)N-(5-(5-(4,5-dihydro-lH-imidazol-2-yl)-lH-benzo[d]imidazol-l-yl)-2',4'-
difluoro-[ 1,1 '-biphenyl]-3-yl)acetamide
A mixture ofN-(5-((2-amino-4-(4,5-dmydro-lH-imidazol-2-yl)phenyl)amino)-
2',4'-difluoro-[l,r-biphenyl]-3-yl)acetamide (80 mg, 0.19 mmol) and formic acid (3 ml)
was heated at 100 °C for 4 h. The formic acid was distilled off under reduced pressure
and the crude was extracted with in ethyl acetate. The solvent was distilled off under
reduced pressure and the residue was purified by preparative HPLC to give the title
product in 12 % yield (10 mg). 1H NMR (400 MHz, D20): δ 8.75 (s, 1H), 8.33 (s,
1H),7.96 (s, 1H), 7.84-7.79 (m, 2H), 7.74 (s, 1H), 7.66-7.6 (m, 1H), 7.47 (s, 1H), 7.29-
7.23 (m, 1H), 7.19-7.14 (m, 1H), 3.99 (m, 4H), 2.06 (s, 3H); LC-MS (ESI): Calculated
mass: 431.44; Observed mass: 432.1 [M+H]+ (RT: 0.36 min).

Example 170.
N-(4'-fluoro-5-(5-(6-fluoropyridin-3-yl)-lH-benzo[d]imidazol-l-yl)-[l,r-bi-
phenyl]-3-yl)acetamide
The title compound was synthesized using the procedures described in Example
53. LC-MS (ESI): Calculated mass: 440.44; Observed mass: 441.1 [M+H]+ (RT: 1.57
min).
Example 171.
N-(3-(5-(l-Ethyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-
yl)phenyl)acetamide
To a solution of N-(3-(5-bromo-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)
phenyl) acetamide of Example 87(g) (1.5 g, 3.8 mmol) in 1,2-dimethoxy ethane (40 ml),
l-ethyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole of Intermediate
Example 13 (1.68 g, 7.59 mmol, 2 eq.), sodium carbonate (1 g, 9.5 mmol, 2.5 eq.) and
water (4 ml) were added and the mixture was degassed for 15 min (N? bubbling).
Pd(PPh3)4 (0.9 g, 0.76 mmol, 0.2 eq.) was added and the mixture was heated at 100 °C
for 2 h. The reaction mixture was quenched by the addition of water (100 ml) and the
organic phase was separated. The aqueous phase was extracted with ethyl acetate (2 x
75 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified column chromatography afford the title compound in 74 % yield (1.15 g).
1H NMR (300 MHz, DMSO-4): δ 8.86 (m, 1H), 8.26 (m, 1H), 7.99-7.94 (m, 2H), 7.87-
7.80 (m, 2H), 7.72-7.60 (m, 3H), 7.39 (s, 2H), 6.31 (s, 2H), 4.15 (quartet, 2H), 2.10 (s,
3H), 1.40 (t, 3H); LC-MS (ESI): Calculated mass: 410.47; Observed mass: 411.2
[M+H]+(RT: 1.11 min).
Example 172.
N-(3 -(5 -(1 -Ethyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1 H-pyrrol-1 -
yl)phenyl)ethanesulfonamide

a) 3-(5-(1 -Ethyl-1 H-pyrazol-4-yl)-1 H-benzo[djimidazol-1 -yl)-5-( 1 H-pyrrol-1 -
yl)aniline
A mixture of 20 % NaOH (5 ml) and N-(3-(5-(l-ethyl-lH-pyrazol-4-yl)-lH-
benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)acetamide of Example 171 (0.9 g,
2.12 mmol) in 25 ml of ethanol was heated at 90 °C for 2 h. The mixture was diluted
with ethyl acetate (100 ml) and the organic layer was washed with water (50 ml) and
brine (25 ml). The solvent was removed under reduced pressure and the residue was
purified by column chromatography over silica gel to afford the title compound in 78 %
yield (0.7 g).
b) N-(3-(5-( 1 -Ethyl-1 H-pyrazol-4-yl)-1 H-benzo [d]imidazol-1 -yl)-5-( 1 H-pyrrol-
1 -yl)phenyl)ethanesulfonamide
To a solution of 3-(5-(l-ethyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-
(1 H-pyrrol-l-yl)aniline (75 mg, 0.2 mmol) in DCM (1 ml) were added pyridine (0.5 ml)
and ethanesulfonyl chloride (52 mg, 0.4 mmol, 2 eq.) and the mixture was stirred at
room temperature for 12 h. Pyridine was removed under reduced pressure and the
residue was purified by preparative HPLC to afford the title compound in 25 % yield
(23 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.31 (s, 1H), 8.74 (s, 1H), 8.26 (s, 1H),
7.98 (d, 2H),7.69-7.61 (m, 3H), 7.42-7.38 (m, 4H), 6.33 (s, 2H), 4.15 (quartet, 2H), 3.16
(quartet, 2H), 1.43 (t, 3H), 1.25 (t, 3H); LC-MS (ESI): Calculated mass: 460.55;
Observed mass: 461.18 [M+H]+ (RT: 1.38 min).
Example 173.
N-(3 -(5 -(1 -Isopropyl-1 H-pyrazol-4-yl)-1 H-benzo[d] imidazol-1 -yl)-5-( 1 H-pyrrol-
1 -yl)phenyl)acetamide
The compound was prepared from the compound of Intermediate Example 12
using the procedure described in Example 171. 1H NMR (300 MHz, DMSO-d6): 3 10.40
(s, 1H), 8.67 (s, 1H), 8.29 (s, 1H), 8.01 (s, 1H), 7.94 (s, 1H), 7.86-7.81 (m, 2H), 7.70-

7.59 (m, 3H), 7.41 (s, 2H), 6.32 (s, 2H), 4.53-4.49 (m, 1H), 2.12 (s, 3H), 1.46 (d, 6H);
LC-MS (ESI): Calculated mass: 424.5; Observed mass: 425.2 [M+H]+ (RT: 1.34 min).
Example 174.
N-(3 -(5 -(1 -Isopropyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-5-( 1 H-pyrrol-
1 -yl)phenyl)methanesulforiarnide
a) 3-(5-(l-lsopropyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-
1 -yl)aniline
A mixture of 20 % NaOH (5 ml) and N-(3-(5-(l-isopropyl-1 H-pyrazol-4-yl)-1H-
benzo[d]imidazol-l-yl)-5-(lH-pyrrol-l-yl)phenyl)acetamide of Example 173 (1 g, 2.43
mmol) in 25 ml ethanol was heated at 90 °C for 2 h. The mixture was diluted with ethyl
acetate (100 ml) and the organic layer was washed with water (50 ml) and brine (25 ml).
The solvent was removed under reduced pressure and the crude was purified by column
chromatography over silica gel to afford the title compound in 93 % yield (0.75 g).
b) N-(3-(5 -(1 -Isopropyl-1 H-pyrazol-4-yl)-1 H-benzo[d] imidazol-1 -yl)-5-( 1H-
pyrrol-1 -yl)phenyl)methanesulfonamide
To a solution of 3-(5-(l-isopropyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-
5-(lH-pyrrol-l-yl)aniline (100 mg, 0.26 mmol) in DCM (1 ml) were added pyridine (0.5
ml) and ethanesulfonyl chloride (60 mg, 0.52 mmol, 2 eq.) and the mixture was stirred
at room temperature for 12 h. Pyridine was removed under reduced pressure and the
residue was purified by preparative HPLC to afford the title compound in 8 % yield (10
mg). 1HNMR(300 MHZ, CD3OD): δ 9.20 (s, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.94 (s,
1H), 7.80 (s, 2H), 7.62 (s, 1H), 7.49 (m, 2H), 7.31 (m, 2H), 6.35 (m, 2H), 4.65-4.51 (m,
1H), 3.14 (s, 3H), 1.55 (d, 6H); LC-MS (ESI): Calculated mass: 461.0; Observed mass:
460.55 [M+H]+ (RT: 1.44 min).
Example 175.

N-(3-(5-(l-isopropyl-lH-pyrazol-4-yl)-lH-benzo[d]imidazol-l-yl)-5-(lH-pyrrol-
1 -yl)phenyl)ethanesulfonamide
The compound was prepared from the compound of Example 173 using the
procedure described in Example 174. 1H NMR (300 MHz, CD3OD): 6 9.05 (s, 1H), 8.16
(s, 1H), 7.99-7.93 (m, 2H), 7.77 (s, 2H), 7.58 (s, IH), 7.47 (m, 2H), 7.30 (m, 2H), 6.35
(m, 2H), 4.60-4.51 (m, IH), 3.30 (quartet, 2H), 1.56-1.54 (d, 6H), 1.38 (t, 3H); LC-MS
(ESI): Calculated mass: 474.58; Observed mass: 475.1 [M+H]+ (RT: 1.50 min).
Example 176.
N-(2',4'-difluoro-5-(6-(l-methyl-lH-pyrazol-4-yl)-3H-imidazo[4,5-b]p>Tidin-3-
yl)-[l,l'-biphenyl]-3-yl)propionamide
To a solution of propionic acid (20 mg, 0.274 mmol) in DMF (2 ml) was added
HATU (155 mg, 0.41 mmol, 1.5 eq.) and the mixture was stirred at room temperature
for 0.5 h. 2':4'-Difluoro-5-(6-(l-methyl-lH-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-
yl)biphenyl-3-amine (110 mg, 0.274 mmol) of Example 132(a) and DIPEA (0.15 ml,
0.821 mmol, 3 eq.) were added and the mixture was stirred for 12 h, quenched with
water and extracted with DCM (3 * 50 ml). The combined organic layer was washed
with water to obtain precipitate which was filtered. The crude product was purified by
preparative HPLC to give the title product (14 mg). *H NMR (400 MHz, DMSO-d6): δ
10.23 (s, IH), 8.92 (s, IH), 8.72 (d, IH), 8.41 (d, IH), 8.33-8.31 (m, 2H), 8.04 (d, IH),
7.89 (d, IH), 7.75-7.69 (m, 2H), 7.48-7.42 (m, IH), 7.29-7.25 (m, IH), 3.90 (s, 3H),
2.40 (quartet, 2H), 1.11 (t, 3H); LC-MS (ESI): Calculated mass: 458.46; Observed
mass: 459.1 [M+H]+ (RT: 1.44 min).
Example 177.
N-(2',4'-difluoro-5-(6-(l-methyl-lH-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-
yl)-[l,l'-biphenyl]-3-yl)cyclopropanecarboxamide
The compound was prepared using the procedure described in Example 176. 1H
NMR (400 MHz, DMSO-d6): g 10.62 (s, IH), 8.94 (s, IH), 8.72 (d, IH), 8.41 (d, IH),

8.31 (d, 2H), 8.04 (s, 1H), 7.88 (br s, 1H), 7.72-7.68 (m, 2H), 7.47-7.41 (m, 1H), 7.29-
7.25 (m. 1H), 3.89 (s, 3H), 1.85 (m, 1H), 0.84 (d, 4H); LC-MS (ESI): Calculated mass:
470.4; Observed mass: 471.1 [M+H]+ (RT: 1.52 min).
Example 178.
N-(2',4'-difluoro-5-(6-(6-fluoropyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-
[ 1,1 '-biphenyl] -3-yl)acetamide
A solution of N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluorobi-
phenyl-3-yl)acetamide of Example 131(c) (330 mg, 0.75 mmol) in 1,2-dimethoxyethane
(10 ml) was degassed by N2 bubbling for 5 min. (6-Fluoropyridin-3-yl)boronic acid (130
mg, 0.9 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min.
Pd(dppf)Cl2 (120 mg, 0.15 mmol, 0.2 eq.) and aqueous sodium carbonate (290 mg, 2.7
mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min
and then heated at 100 °C for 5 h. The reaction mixture was quenched with water and
extracted with ethyl acetate (3x50 ml). The combined organic layer was washed with
water, brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure and the residue was purified by preparative HPLC to give the title product. 1H
NMR (400 MHz, DMSO-d6): δ 10.40 (s, 1H), 9.03 (s, 1H), 8.79 (d, 1H), 8.68 (s, 1H),
8.60 (s, 1H), 8.43 (dt, 1H), 8.30 (s, 1H), 7.87 (s, 1H), 7.70 (s, 2H), 7.47-7.26 (m, 3H),
2.07 (s, 3H); LC-MS (ESI): Calculated mass: 459.4; Observed mass: 460.1 [M+H]+
(RT: 1.53 min).
Example 179.
N-(5-(6-(lH-pyrazol-l-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2'-fluoro-4'-methoxy-
[1,1 '-biphenyl] -3 -yl)acetamide
a) yV-(2'-fluoro-4'-methoxy-5-nitro-[l, 1 '-biphenyl]-3-yl)acetamide
A solution of N-(3-bromo-5-nitrophenyl)acetamide (0.8 g, 3.089 mmol) in 1,2-
dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. (2-Fluoro-4-methoxy-
phenyl)boronic acid (0.63 g, 3.71 mmol, 1.2 eq.) was added and the mixture was

degassed for another 5 min. Pd(dppf)Cl2 (0.3 g, 0.371 mmol, 0.12 eq.) and aqueous
sodium carbonate (0.65 g, 6.18 mmol, 2.0 eq.) were added sequentially and the reaction
mixture was further degassed for 5 min and then heated at 90 °C for 4 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 97 % yield (0.91 g).
b) N-(5-amino-2'-fluoro-4'-methoxy-[l, 1 '-biphenyl]-3-yl)acetamide
To a solution of N-(2'-fluoro-4'-methoxy-5-nitro-[l,l'-biphenyl]-3-yl)acetamide
(0.9 g, 2.96 mmol) in THF (10 ml) and methanol (10 ml) were added a solution of
ammonium chloride (0.63 g, 11.83 mmol, 4 eq.) in water (10 ml) and zinc (0.77 g, 11.83
mmol, 4 eq.). The mixture was stirred at room temperature for 12 h and filtered. The
filtrate was diluted with water and extracted with ethyl acetate (3 x 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure to afford the title product in 97 %
yield (790 mg). 1H NMR (300 MHz, DMSO-d6): δ 9.73 (s, 1H), 7.28 (t, 1H), 6.91-6.78
(m, 4H), 6.34 (s, 1H), 5.15 (s, 2H), 3.77 (s, 3H), 1.98 (s, 3H); LC-MS (ESI): Calculated
mass: 274.2; Observed mass: 275.2 [M+H]+ (RT: 0.34 min).
c)N-(5-((5-bromo-3-nitropyridin-2-yl)amino)-2'-fluoro-4'-methoxy-[l,r-bi-
phenyl]-3-yl)acetamide
A solution of N-(5-amino-2'-fluoro-4'-methoxy-[l ,l'-biphenyl]-3-yl)acetamide
(2.5 g, 9.124 mmol), 5-bromo-2-chloro-3-nitropyridine (2.0 g, 9.124 mmol, 1.0 eq.) and
potassium fluoride (0.53 g, 9.124 mmol, 1.0 eq.) in DMF (8 ml) was heated at 130 °C
for 5 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue

was purified by column chromatography (60-120 silica gel, 2 % methanol in DCM) to
give the title product in 94 % yield (4.1 g).
d)N-(5-((3-amino-5-bromopyridin-2-yl)amino)-2'-fluoro-4'-methoxy-[l,r-bi-
phenyl] -3 -y l)acetamide
To a solution of N-^-^S-bromo-S-nitropyridin^-yOamino^'-fluoro^'-
methoxy-[l,l'-biphenyl]-3-yl)acetamide (4.0 g, 8.421 mmol) in THF (50 ml) and
methanol (5 ml) were added a solution of ammonium chloride (0.893 g, 16.842 mmol, 2
eq.) in water (15 ml) and zinc (1.06 g, 16.842 mmol, 4 eq.). The mixture was stirred at
room temperature for 3 h and filtered. The filtrate was diluted with water and extracted
with ethyl acetate (3 * 100 ml). The combined organic layer was washed with water,
brine and dried over sodium sulphate. The solvent was distilled off under reduced
pressure to afford the title product in 85 % yield (3.21 g).
e)N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-2'-fluoro-4'-methoxy-[l,r-bi-
phenyl] -3 -yl)acetamide
A mixture ofN-(5-((3-amino-5-bromopyridin-2-yl)amino)-2'-fluoro-4'-methoxy-
[l,l'-biphenyl]-3-yl)acetamide (3.2 g, 7.19 mmol) and formic acid (2 ml) was heated at
90 °C for 1 h. Formic acid was then distilled off under reduced pressure and the crude
was dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 91 % yield (3.0 g). [H NMR (300 MHz, DMSO-d6): δ 10.36
(s, 1H), 8.99 (s, 1H), 8.55 (s, 1H), 8.18 (s, 1H), 8.86 (s, 1H), 7.62-7.53 (m, 3H), 7.03-
6.92 (m, 2H), 3.83 (s, 3H), 2.11 (s, 3H); LC-MS (ESI): Calculated mass: 455.8;
Observed mass: 457.0 [M+H]+ (RT: 1.58 min).
f)N-(5-(6-(lH-pyrazol-l-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2'-fluoro-4'-
methoxy- [ 1, l'-biphenyl]-3 -yl)acetamide

A solution of N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-2'-fluoro-4'-
methoxy-[l,r-biphenyl]-3-yl)acetamide ( 250 mg, 0.549 mmol) in DMF (1.5 ml) were
added pyrazole (75 mg, 1.1 mmol, 2.0 eq), copper(I) oxide (94 mg, 0.66 mmol, 1.2 eq.)
and cesium carbonate (358 mg, 1.1 mmol, 2.0 eq.) and the mixture was heated at 120 °C
for 12 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by column chromatography (neutral alumina, 1 % methanol in DCM) to
give the title product in 82 % yield (200 mg). *H NMR (400 MHz, DMSO-d6): δ 10.39
(s, 1H), 9.05 (s, 1H), 9.02 (d, 1H), 8.67 (d, 2H), 8.26 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H),
7.68 (s, 1H), 7.59 (t, 1H), 7.04-6.95 (m, 2H), 6.64 (t, 1H), 3.85 (s, 3H), 2.13 (s, 3H);
LC-MS (ESI): Calculated mass: 442.45; Observed mass: 443.1 [M+H]+ (RT: 1.42 min).
Example 180.
N-(2'-fluoro-4'-methoxy-5-(6-(l-methyl-lH-pyrazol-4-yl)-3H-imidazo[4,5-
b]pyridin-3-yl)- [1,1 '-biphenyl] -3 -yl)acetamide
A solution of N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-2'-fluoro-4'-
methoxy-[l,l'-biphenyl]-3-yl)acetamide of Example 179(e) (250 mg, 0.549 mmol) in
1,2-dimethoxyethane (10 ml) was degassed by N2 bubbling for 5 min. l-Methyl-4-
(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (137 mg, 0.66 mmol, 1.2 eq.)
was added and the mixture was degassed for another 5 min. Pd(PPli3)4 (63 mg, 0.0549
mmol, 0.1 eq.) and aqueous sodium carbonate (117 mg, l.l mmol, 2.0 eq.) were added
sequentially and the mixture was further degassed for 5 min and then heated at 100 °C
for 5 h. The reaction mixture was quenched with water and extracted with ethyl acetate
(3 x 50 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure and the residue
was purified by preparative HPLC to give the title product in 90 % yield (225 mg). *H
NMR (400 MHz, DMSO-<50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 40 % ethyl acetate in hexane) to
give the title product in 73 % yield (1.1 g). lU NMR (300 MHz, DMSO-4): δ 10.41 (s,
1H), 9.02 (s, 1H), 8.52 (d, 1H), 8.33 (d, 1H), 8.21 (s, 1H), 7.91 (s, 1H), 7.73-7.64 (m,
2H), 7.43 (m, 1H), 7.26 (m, 1H), 2.11 (s, 3H), 0.27 (s, 9H); LC-MS (ESI): Calculated
mass: 460.55; Observed mass: 461.2 [M+H]+ (RT: 1.83 min).

e)N-(5-(6-ethynyl-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluoro-[l,l'-biphenyl]-
3-yl)acetamide IN2495-050
To a solution of N-(2',4'-difluoro-5-(6-((trimethylsilyl)ethynyl)-3H-imidazo[4,5-
b]pyridin-3-yl)-[l,r-biphenyl]-3-yl)acetamide (1.1 g, 2.4 mmol) in THF at 0°C was
added TBAF (1 M in THF; 0.6 ml, 2.4 mmol, 1.0 eq.) and the mixture was stirred for
0.5 h. The mixture was filtered over a pad of silica and distilled to give crude residue
which was purified by column chromatography (60-120 silica gel, 5 % methanol in
chloroform) to give the title product in 86 % yield (0.8 g). 1H NMR (300 MHz, DMSO-
d6): δ 10.39 (s, 1H), 9.03 (s, 1H), 8.56 (d, 1H), 8.38 (d, 1H), 8.23 (s, 1H), 7.91 (s, 1H),
7.75-7.66 (m, 2H), 7.48-7.41 (m, 1H), 7.30-7.24 (m, 1H), 4.39 (s, 1H), 2.07 (s, 3H); LC-
MS (ESI): Calculated mass: 388.3; Observed mass: 389.2 [M+H]+ (RT: 1.49 min).
f)N-(2',4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l)2,3-triazol-4-yl)-3H-
imidazo[4,5-b]pyridin-3-yl)-[l,l'-biphenyl]-3-yl)acetamide
A mixture of 7Y-(5-(6-ethynyl-3H-imidazo[4,5 -b]pyridin-3-yl)-2',4'-difiuoro-[1,1'-
biphenyl]-3-yl)acetamide (0.5 g, 1.28 mmol), 4-azido-l-methylpiperidine of
Intermediate Example 11 (0.21 g, 1.54 mmol, 1.2 eq.), sodium ascorbate (0.25 g, 1.28
mmol, 1.0 eq.) and copper sulfate pentahydrate (0.16 g, 0.6 mmol, 0.5 eq.) in DMSO,
DCM and water (2:5:2, 9 ml) was stirred for 12 h at room temperature. The mixture was
quenched with water and the precipitate formed was filtered and dried to give the crude
product which was purified by preparative HPLC to give the title product in 74 % yield
(0.5 g). 1HNMR (300 MHz, CDCI3): δ 8.94 (d, 1H), 8.56 (d, 1H), 8.43 (s, 1H), 8.15 (s,
1H), 7.90 (s, 1H), 7.72 (s, 1H), 7.65 (s, 2H), 7.53-7.45 (m, 1H), 7.05-7.49 (m, 1H), 4.68-
4.59 (m, 1H), 3.18-3.13 (m, 4H), 2.62 (s, 3H), 2.44-2.39 (m, 4H), 2.24 (s, 3H); LC-MS
(ESI): Calculated mass: δ58.50; Observed mass: δ29.2 [M+H] + (RT: 0.39 min).
Example 182.
N-(2',4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-3H-
imidazo[4,5-b]pyridin-3-yl)-[l,l'-biphenyl]-3-yl)ethanesulfonamide

a)2';4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-3H-
imidazo [4,5-b]pyridin-3-yl)- [1,1 '-biphenyl] -3-amine
N-(2',4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-3H-
imidazo[4,5-b]pyridin-3-yl)-[l,l'-biphenyl]-3-yl)acetamide of Example 181 (0.4 g,
0.757 mmol) was added to aqueous 6 N HC1 (10 ml) at 0 °C and the reaction mixture
was stirred at 70 °C for 3 h. The reaction mixture was quenched with saturated aqueous
sodium bicarbonate soluition and extracted with ethyl acetate (3 x 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate
and the residue was purified by column chromatography (60-120 silica gel, 10 %
methanol in DCM) to give the title product in 30 % yield (0.11 g). LC-MS (ESI):
Calculated mass: 486.52; Observed mass: 487.3 [M+H]+ (RT: 0.22 min).
b)N-(2',4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl)-3H-
imidazo[4,5-b]pyridin-3-yl)-[l, 1 '-biphenyl]-3-yl)ethanesulfonamide
To a solution of 2',4'-difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-triazol-
4-yl)-3H-imidazo[4,5-b]pyTidin-3-yl)-[l,T-biphenyl]-3-amine (55 mg, 0.113 mmol) in
DCM was added pyridine (17 mg, 0.226 mmol, 2.0 eq.) followed by ethanesulfonyl
chloride (17 mg, 0.135 mmol, 1.2 eq.). The reaction was monitored by LCMS. After
completion of the reaction the solvent was removed under reduced pressure and the
crude product was purified by preparative HPLC to give the title product in 46 % yield
(30 mg). 1HNMR (300 MHz, DMSO-d6): 6 10.31 (s, 1H), 9.01 (s, 1H), 8.97 (d, 1H),
8.84 (s, 1H), 8.62 (s, 1H), 7.93 (s, 1H), 7.75-7.71 (m, 2H), 7.48-7.41 9 (m, 2H), 7.27 (m,
1H), 3.45 (m, 1H), 2.79 (s, 3H), 2.41-2.34 (m, 4H), 2.28-2.24 (quartet, 2H), 1.27-1.22
(m, 4H), 1.03 (t, 3H); LC-MS (ESI): Calculated mass: δ78.64; Observed mass: δ78.9
[M+Hf (RT: 0.11 min).
Example 183.
N-(2',4'-difiuoro-5-(6-( 1 -(1 -methylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-3H-
imidazo [4,5 -b]pyridin-3 -yl)- [ 1,1 '-biphenyl] -3 -yl)cyclopropanecarboxamide

To a solution of cyclopropanecarboxylic acid (14 mg, 0.169 mmol, 1.5 eq.) in
DMF (2 ml) was added HATU (90 mg, 0.226 mmol, 2.0 eq.) and the mixture was stirred
at room temperature for 0.5 h. 2',4'-Difluoro-5-(6-(l-(l-methylpiperidin-4-yl)-lH-l,2,3-
triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-[l,r-biphenyl]-3-amine of Example 182(a)
(55 mg, 0.113 mmol) and DTPEA (45 mg, 0.339 mmol, 3 eq.) were added and the
mixture was stirred for 12 h, quenched with water and extracted with DCM (3 * 50 ml).
The combined organic layer was washed with water to obtain precipitate which was
filtered. The crude product was purified by preparative HPLC to give the title product in
13 % yield (12 mg). 1H NMR (300 MHz, DMSO-d6): δ 10.68 (s, 1H), 8.98 (s, 2H), 8.83
(s, 1H), 8.62 (s, 1H), 8.33 (s, 1H), 8.88 (s, 1H), 7.71-7.66 (m, 2H), 7.46-7.39 (m, 1H),
7.28-7.23 (m, 1H), 4.83 (m, 1H), 3.62-3.52 (m, 4H), 2.81 (s, 3H), 2.30-2.26 (m, 4H),
1.85 (m, 1H), 0.83 (d, 4H); LC-MS (ESI): Calculated mass: δ54.59; Observed mass: δ54.9 [M+H]+ (RT: 0.183 min).
Example 184.
N-(5-(5-(lH-pyrazol-l -yl)-1 H-benzo[d]imidazol-1 -yl)-2',6'-difluoro- [1,1 '-bi-
phenyl] -3 -yl)methanesulfonamide
a)5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',6'-difluoro-[l,l'-bi-
phenyl]-3-amine
To a solution of N-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',6'-di-
fluorobiphenyl-3-yl)acetamide of Example 152 (2.1 g, 4.895 mmol) in ethanol (50 ml)
was added 10 % aqueous solution of NaOH (10 ml) and the mixture was heated at 100
°C for 2 h. The reaction mixture was quenched with water and extracted with ethyl
acetate (3 x 50 ml). The combined organic layer was washed with water, brine and dried
over sodium sulphate. The solvent was distilled off under reduced pressure to afford the
title product in 89 % yield (1.6 g).
b)N-(5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',6'-difluoro-[l,l'-bi-
phenyl]-3-yl)methanesulfonamide

To a solution of 5-(5-(lH-pyrazol-l-yl)-lH-benzo[d]imidazol-l-yl)-2',6'-di-
fluoro-[l,r-biphenyl]-3-amine (50 mg, 0.129 mmol) inDCM was added pyridine (20
mg, 0.258 mmol, 2.0 eq.) followed by methanesulfonyl chloride (18 mg, 0.155 mmol,
1.2 eq.). The reaction was monitored by LCMS. After completion of the reaction the
solvent was removed under reduced pressure and the crude product was purified by
preparative HPLC to give the title product in 50 % yield (30 mg). *H NMR (400 MHz,
DMSO-d6): δ 10.32 (s, 1H), 8.76 (s, 1H), 8.61 (d, 1H), 8.24 (d, 1H), 7.93 (dd, 1H), 7.79
(s, 1H), 7.76 (d, 1H), 7.61-7.57 (m, 4H), 7.37 (s, 1H), 7.31 (t, 2H), 3.19 (s, 3H); LC-MS
(ESI): Calculated mass: 465.48; Observed mass: 466.1 [M+H]+ (RT: 1.47 rain).
Example 185.
N-(5-(5 -(1 H-pyrazol-1 -yl)-1 H-benzo[d]imidazol-1 -yl)-2',6'-difluoro- [1,1'-
biphenyl]-3-yl)ethanesulfonamide
The compound was prepared from the compound of Example 152 using the
procedure described in Example 184. 1H NMR (400 MHz, DMSO-ef6): δ 10.35 (s, 1H),
8.72 (s, 1H), 8.60 (d, 1H), 8.24 (d, 1H), 7.93 (dd, 1H), 7.76 (t, 2H), 7.61-7.54 (m, 3H),
7.39 (s, 1H), 7.31 (t, 2H), 6.56 (t, 1H), 2.40 (quartet, 2H), 1.26 (t, 3H); LC-xMS (ESI):
Calculated mass: 479.5; Observed mass: 480.0 [M+H]+ (RT: 1.51 min).
Example 186.
N-(2',6'-difiuoro-5-(5-(l -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl>
[1,1 '-biphenyl]-3-yl)methanesulfonamide
a) 2',6'-difluoro-5-(5-(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo[d]imidazol-1 -yl)-
[1,1 '-biphenyl] -3 -amine
To a solution of N-(2',6'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)biphenyl-3-yl)acetamide of Example 151 (2.0 g, 4.514 mmol) in ethanol
(50 ml) was added 10 % aqueous solution of NaOH (2.5 ml) and the mixture was heated
at 100 °C for 2 h. The reaction mixture was quenched with water and extracted with

ethyl acetate (3 * 50 ml). The combined organic layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 99 % yield (1.8 g).
b) N-(2',6'-difluoro-5-(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-
[l,l'-biphenyl]-3-yl)methanesulfonamide
To a solution of 2',6'-difluoro-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-l-yl)-[l,l'-biphenyl]-3-amine (50 mg, 0.124 mmol) in DCM was added
pyridine (20 mg, 0.258 mmol, 2.0 eq.) followed by methanesulfonyl chloride (29 mg,
0.155 mmol, 2.0 eq.). The reaction was monitored by LCMS. After completion of the
reaction the solvent was removed under reduced pressure and the crude product was
purified by preparative HPLC to give the title product in 42 % yield (25 mg). 1H NMR
(300 MHz, DMSO-de): δ 10.34 (s, 1H), 8.76 (s, 1H), 8.22 (s, 1H), 7.97 (d, 2H), 7.66-
7.57 (m, 5H), 7.36-7.30 (m, 3H), 3.88 (s, 3H), 3.19 (s, 3H); LC-MS (ESI): Calculated
mass: 479.50; Observed mass: 480.2 [M+H]+(RT: 1.27min).
Example 187.
N-(2',6'-difluoro-5 -(5 -(1 -methyl-1 H-pyrazol-4-yl)-1 H-benzo [d] imidazol-1 -yl)-
[1,1 '-biphenyl]-3-yl)ethanesulfonamide
The compound was prepared from the compound of Example 151 using the
procedure described in Example 186. 1H NMR (400 MHz, DMSO-d6): δ 10.37 (s, 1H),
8.80 (s, 1H), 8.23 (s, 1H), 7.98 (d, 2H), 7.67 (s, 2H), 7.61 (s, 1H), 7.56 (s, 2H), 7.38 (s,
1H), 7.30 (t, 2H), 3.88 (s, 3H), 3.30 (quartet, 2H), 1.26 (t, 3H); LC-MS (ESI):
Calculated mass: 493.3; Observed mass: 494.1 [M+H]+ (RT: 1.38 min).
Example 188.
N-(4'-fluoro-2'-methoxy-5-(5-(l -methyl- lH-pyrazol-4-yl)-lH-benzo[d]imidazol-
1 -yl)- [1,1 '-biphenyl] -3-yl)acetamide
a)N-(4'-fluoro-2'-methoxy-5-nitro-[l,r-biphenyl]-3-yl)acetamide

A solution of iV-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (0.8 g, 3.089
mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. (4-
Fluoro-2-methoxyphenyl)boronic acid (0.63 g, 3.71 mmol, 1.2 eq.) was added and the
mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.3 g, 0.371 mmol, 0.12 eq.) and
aqueous sodium carbonate (0.65 g, 6.18 mmol, 2.0 eq.) were added sequentially and the
mixture was further degassed for 5 min and then heated at 90 °C for 4 h. The mixture
was quenched with water and extracted with ethyl acetate (3 x 50 ml). The combined
organic layer was washed with water, brine and dried over sodium sulphate. The solvent
was distilled off under reduced pressure and the residue was purified by column
chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the title
product in 97 % yield (0.91 g). 1H NMR (300 MHz, DMS(W6): δ 10.51 (s, 1H), 8.63 (s,
1H), 7.98 (d, 2H), 7.44 (t, 1H), 7.23 (d, 1H), 6.95 (dt, 1H), 3.86 (s, 3H), 2.14 (s, 3H);
LC-MS (ESI): Calculated mass: 304.2; Observed mass: 305.0 [M+H]+ (RT: 1.57 min).
b) N-(5-amino-4'-fmoro-2'-methoxy-[ 1,1 '-biphenyl]-3-yl)acetamide
To a solution of N-(4'-fluoro-2'-methoxy-5-nitro-[l,l'-biphenyl]-3-yl)acetamide
(0.9 g, 2.96 mmol) in THF (10 ml) and methanol (10 ml) were added a solution of
ammonium chloride (0.63 g, 11.83 mmol, 4 eq.) in water (10 ml) and zinc (0.77 g, 11.83
mmol, 4 eq.). The mixture was stirred at room temperature for 12 h and filtered. The
filtrate was diluted with water and extracted with ethyl acetate (3 * 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure to give the title product in 97 %
yield (790 mg). 1H NMR (300 MHz, DMSO-4): δ 9.68 (s, 1H), 7.21 (t, 1H), 7.02-6.96
(m, 2H), 6.87-6.80 (m, 1H), 6.73 (s, 1H), 6.32 (s, 1H), 5.15 (br s, 2H), 3.79 (s, 3H), 2.03
(s, 3H).
c)N-(5-((4-bromo-2-nitrophenyl)amino)-4'-fluoro-2'-methoxy-[l,r-biphenyl]-3-
yl)acetamide

A solution of N-(5-amino-4'-fluoro-2'-methoxy-[l, 1 '-biphenyl]-3-yl)acetamide
(0.5 g, 1.83 mmol), 4-bromo-l-fluoro-2-nitrobenzene (0.4 g, 1.83 mmol) and potassium
fluoride (0.106 g, 1.83 mmol, 1.0 eq.) in DMF (10 ml) was heated at 130 °C for 5 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 2 % methanol in DCM) to give
the title product in 94 % yield (0.8 g). 1H NMR (300 MHz, DMSO-4): δ 10.03 (s, 1H),
9.42 (s, 1H), 8.23 (s, 1H), 7.70-7.63 (m, 2H), 7.43 (s, 1H), 7.35-7.23 (m, 2H), 7.05 (s,
1H), 7.02 (s, 1H), 6.86 (t, 1H), 3.81 (s, 3H), 2.06 (s, 3H).
d)N-(5-((2-amino-4-bromophenyl)amino)-4'-fluoro-2'-methoxy-[l,r-biphenyl]-
3-yl)acetamide
To a solution of N-(5-((4-bromo-2-nitrophenyl)amino)-4'-fluoro-2'-methoxy-
[l,l'-biphenyl]-3-yl)acetamide (0.8 g, 1.69 mmol) in THF (30 ml) and methanol (30 ml)
were added a solution of ammonium chloride (0.18 g, 3.34 mmol, 2 eq.) in water (15
ml) and zinc (0.21 g, 3.34 mmol, 2 eq.). The mixture was stirred at room temperature
for 3 h and filtered. The filtrate was diluted with water and extracted with ethyl acetate
(3 x 100 ml). The combined organic layer was washed with water, brine and dried over
sodium sulphate. The solvent was distilled off under reduced pressure to afford the title
product in 96 % yield (96 g). 1H NMR (300 MHz, DMSO-d6): § 9.77 (s, 1H), 7.20 (t,
2H), 7.03-6.94 (m, 4H), 6.90 (d, 1H), 6.81 (m, 1H), 6.64 (dd, 1H), 6.5 (s, 1H), 5.08 (br
s, 2H), 3.76 (s, 3H), 1.99 (s, 3H); LC-MS (ESI): Calculated mass: 444.3; Observed
mass: 445.9[M+H]+ (RT: 1.66 tnin).
e) N-(5 -(5 -bromo-1 H-benzo [d] imidazol-1 -yl)-4'-fluoro-2'-methoxy- [1,1'-
biphenyl]-3 -yl)acetamide
A mixture ofN-(5-((2-amino-4-bromophenyl)amino)-4'-fiuoro-2'-methoxy-[l,r-
biphenyl]-3-yl)acetamide (0.7 g, 1.58 mmol) and formic acid (10 ml) was heated at 90
°C for 1 h. Formic acid was then distilled off under reduced pressure and the residue was

dissolved in ethyl acetate. The ethyl acetate layer was washed with water, brine and
dried over sodium sulphate. The solvent was distilled off under reduced pressure to
afford the title product in 97 % yield (0.7 g). 1HNMR (300 MHz, DMSO-d6): § 10.33
(s, 1H), 8.69 (s, 1H), 7.9 (d, 2H), 7.67 (t, 2H), 7.54-7.40 (m, 3H), 7.08 (dd, 1H), 6.91
(dt, 1H), 3.84 (s, 3H), 2.10 (s, 3H): LC-MS (ESI): Calculated mass: 454.3; Observed
mass 456.0 [M+H]+ (RT: 1.66 min).
f)N-(4'-fluoro-2'-methoxy-5-(5-(l-methyl-lH-pyrazol-4-yl)-lH-benzo[d]-
imidazol-1 -yl)- [1,1 '-biphenyl] -3-yl)acetamide
A solution of N-(5-(5-bromo-lH-benzo[d]imidazol-l-yl)-4'-fiuoro-2'-methoxy-
[l,l'-biphenyl]-3-yl)acetamide (250 mg, 0.551 mmol) in 1,2-dimethoxyethane (10 ml)
was degassed by N2 bubbling for 5 min. l-Methyl-4-(4,4,5,5-tetramethyl-l,3,2-
dioxaborolan-2-yl)-lH-pyrazole ( 137 mg, 0.661 mmol, 1.2 eq.) was added and the
mixture was degassed for another 5 min. Pd(dppf)Cl2 (76 mg, 0.066 mmol, 0.12 eq.)
and aqueous sodium carbonate (117 mg, 1.1 mmol, 2.0 eq.) were added sequentially
and the mixture was further degassed for 5 min and then heated at 100 °C for 5 h. The
reaction mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml).
The combined organic layer was washed with water, brine and dried over sodium
sulphate. The solvent was distilled off under reduced pressure and the residue was
purified by column chromatography (60-120 silica gel, 4 % methanol in DCM) to give
the title product in 84 % yield (210 mg). 1H NMR (400 MHz, DMSO-d6): S 10.35 (s,
1H), 8.93 (s, 1H), 8.24 (s, 1H), 8.07 (s, 1H), 7.98 (d, 2H), 7.71-7.69 (m, 3H), 7.47 -7.44
(m, 2H), 7.08 (dd, 1H), 6.93 (dt, 1H), 3.88 (s, 3H), 3.17 (s, 3H), 2.08 (s, 3H); LC-MS
(ESI): Calculated mass: 455.48; Observed mass: 456.1 [M+H]+ (RT: 1.13 min).
Example 189.
N-(5 -(5 -(1 H-pyrazol-1 -yl)-1 H-benzo [d]imidazol-1 -yl)-2'-fluoro-4'-methoxy-
[1,1 '-biphenyl]-3-yl)acetamide
a) N-(2'-fluoro-4'-methoxy-5-nitro-[ 1,1 '-biphenylj-3-yl)acetamide

A solution of A/-(3-bromo-5-nitrophenyl)acetamide of Example 1(c) (0.8 g, 3.089
mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N? bubbling for 5 min. (2-
Fluoro-4-methoxyphenyl)boronic acid (0.63 g, 3.71 mmol, 1.2 eq.) was added and the
mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.3 g, 0.371 mmol, 0.12 eq.) and
aqueous sodium carbonate (0.65 g, 6.18 mmol, 2.0 eq.) were added sequentially and the
mixture was further degassed for 5 min and then heated at 90 °C for 4 h. The reaction
mixture was quenched with water and extracted with ethyl acetate (3 x 50 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure and the residue was purified by
column chromatography (60-120 silica gel, 50 % ethyl acetate in hexane) to give the
title product in 97 % yield (0.91 g). *H NMR (300 MHz, DMSO-d6): δ 10.52 (s, 1H),
8.59 (s, 1H), 8.07 (s, 1H), 7.97 (s, 1H), 7.55 (t, 1H), 7.05-6.93 (m, 2H), 3.84 (s, 3H),
2.11 (s,3H).
b)iV-(5-amino-2'-fluoro-4'-methoxy-[l,T-biphenyl]-3-yl)acetamide
To a solution of N-(2'-fluoro-4'-methoxy-5-nitro-[l,r-biphenyl]-3-yl)acetamide
(0.9 g, 2.96 mmol) in THF (10 ml) and methanol (10 ml) were added a solution of
ammonium chloride (0.63 g, 11.83 mmol, 4 eq.) in water (10 ml) and zinc (0.77 g, 11.83
mmol, 4 eq.). The mixture was stirred at room temperature for 12 h and filtered. The
filtrate was diluted with water and extracted with ethyl acetate (3 x 100 ml). The
combined organic layer was washed with water, brine and dried over sodium sulphate.
The solvent was distilled off under reduced pressure to afford the title product in 97 %
yield (790 mg). 1HNMR (300 MHz, DMSO-