FORM 2 The Patents Act, 1970 (39 of 1970) & The Patent Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) "(lS,5S)-3-(5,6-DICHLORO-3-PYRIDINYL)-3,6-DIAZABICYCLO[3.2.0]HEPTANE" Abbott Laboratories, a company incorporated in the U.S.A. having its Registered Office at Dept. 377 Bldg. AP6A-1, 100 Abbott Park Road, Abbott Park, Illinois 60064-6008, USA. The following specification particularly describes the invention and the manner in which it is to be performed WO 2006/01966(1 PCT/LS2005/024447 (lS,5S)-3-(5,6-DICHLORO-3-PYRlDINYL)-3,6-DlAZABICYCLO(3.2.0]IlEPTANE FIELD OF THE INVENTION The present invention is directed to (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6- 5 diazabicyclo[3.2.0]heptane, salts thereof, and its use to treat pain, in particular, neuropathic pain. BACKGROUND OF THE INVENTION The search for potent and effective analgesics continues to be a significant research 10 goal in the medical community. A substantial number of medical disorders and conditions produce pain as part of the disorder or condition. Relief of this pain is a major aspect of ameliorating or treating the overall disorder or condition. Pain and the possible allievation thereof is also attributable to the individual patient's mental condition and physical condition. Opioid and non-opioid drugs are the two major classes of analgesics (A. Dray and L. 15 Urban, Ann. Rev. Pharmacol. Toxicol., 36:253-280, (1996)). Opioids, such as morphine, act at opioid receptors in the brain to block transmission of the pain signals in the brain and spinal cord (N.I. Cherney, Drug, 51:713-737, (1996)). Non-opioids such as non-steroid anti inflammatory agents (NSATDs) typically, but not exclusively, block the production of prostaglandins to prevent sensitization of nerve endings that facilitate the pain signal to the 20 brain (Dray, et al., Trends in Pharmacol. Sci., 15:190-197, (1994); T.J. Carty and A. Marfat,"COX-2 Inhibitors. Potential for reducing NSATD side-effects in treating inflammatory diseases", Emerging Drugs: Prospect for Improved Medicines. (W. C. Bowman, J.D. Fitzgerald, and J.B. Taylor, eds.), Ashley Publications Ltd., London, Chap. 19., pp. 391- 411). 25 Certain compounds, with primary therapeutic indications other than analgesia, have been shown to be effective in some types of pain control. These are classified as analgesic adjuvants, and include tricyclic antidepressants (TCAs) and some anticonvulsants such as gabapentin (Williams et al., J. Med. Chem., 42:1481-1500 (1999)). They are used increasingly for treatment of pain, especially for pain resulting from nerve injury due to 30 trauma, racllatica, or dicsase. (lS,5S)-3-(5,6-DicUoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, and its salts, are novel compounds that demonstrate utility in treating pain and disorders associated with the 1 WO 2m>f./(M«)6f,0 PCT/US2005/024447 nicotinic acetylcholine receptor (nAChR). (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane, and salts thereof, may also have utility when administered in combination with an opioid such as morphine, a non-steroid anti-inflammatory agent such as aspirin, a tricyclic antidepressant, or an anticonvulsant such as gabapentin or pregabalin for 5 treating pain and disorders associated with the nicotinic acetylcholine receptor. WO 01^81347 discloses diazabicyclo[3.2.0]heptanes that are analgesic agents. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 10 3,6-diazabicyclo[3.2.0]heptane acetate. Figure 1A is the differential scanning calorimetry (DSC) thermogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane acetate. Figure 2 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane hemicitrate. 15 Figure 2A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6- dicMoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane hemicitrate. Figure 3 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dicMoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane methanesulfonate. Figure 3 A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6- 20 dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane methanesulfonate. Figure 4 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane maleate. Figure 4A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6- dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane maleate. 25 Figure 5 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dicbloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane hydrochloride. Figure 5 A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6-dicrdoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane hydrochloride. Figure 6 is the powder X-ray diffractogram of (lS,5S>3-(5,6-dichloro-3-pyridinyl)-30 3,6-diazabicyclo[3.2.0]heptaneL-taitrale. Figure 6A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6-dicUoro-3-pyridmyl)-3,6-diazabicyclo[3.2.0]heptaneL-tertrate. 2 WO 2006/019660 PCT/US2005/024447 Figure 6B is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptaue L-tarlrate monohydrate. Figure 6C is the differential scanning calorimetry thennogram of (lS,5S)-3-(5,6- dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptaneL-tartrate monohydrate. 5 Figure 7 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane 4-methylbenzenesulfonate (Form II). Figure 7A is the differential scanning calorimetry thennogram of (lS,5S)-3-(5,6- dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane 4-memylbenzenesulfonate (Form II). Figure 7B is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 10 3,6-diazabicyclo[3.2.0]heptane 4-methylbenzenesulfonate (Form I). Figure 8 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane sulfate monohydrate. Figure 8A is the powder X-ray diffractogram of (lS>5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane sulfate. 15 Figure 8B is the differential scanning calorimetry thermogram of (1 S,5S)-3-(5,6- dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane sulfate. Figure 9 is the powder X-ray diffractogram of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane. Figure 9A is the differential scanning calorimetry thermogram of (lS,5S)-3-(5,6- 20 dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane. Figures 7,7B, 8, and 9 were determined from the single cell crystal data of then-respective compounds. SUMMARY OF THE INVENTION 25 The present invention discloses (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane or a phaimaceutically acceptable salt or prodrug thereof and its use to treat pain, in particular, neuropathic pain. DETAILED DESCRIPTION OF THE INVENTION 30 In its principle embodiment the present invention discloses (1 S,5 S)-3-(5,6-dichlqro- 3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a phaimaceutically acceptable salt or prodrug thereof. 3 WO 2006/019660 PCT/US2005/024447 In another embodiment, the present invention relates to a method of treating pain including, but not limited to, neuropathic pain comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof. 5 In another embodiment, the present invention relates to a method of treating pain including, but not limited to, neuropathic pain comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof in combination with an opioid including, but not limited to morphine. 10 In another embodiment, the present invention relates to a method of treating pain including, but not limited to, neuropathic pain comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof in combination with a non-steroid anti-inflammatory agent including, but not limited to aspirin. 15 In another embodiment, the present invention relates to a method of treating pain including, but not limited to, neuropathic pain comprising adniinistering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof in combination with an anticonvulsant including, but not limited to, gabapentin or pregabalin. 20 In another embodiment, the present invention relates to a method of treating pain including, but not limited to, neuropathic pain comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof in combination with a tricyclic antidepressant 25 In another embodiment, the present invention relates to a method of treating Alzheimer's disease, Parkinson's disease, memory dysfunction, Tourette's syndrome, sleep disorders, attention deficit hyperactivity disorder, neurodegeneration, inflammation, neuroprotection, anxiety, depression, mania, schizophrenia, anorexia and other eating disorders, AIDS-induced dementia, epilepsy, urinary incontinence, substance abuse, smoking 30 cessation or inflammatory bcv/el cyndrcme, comprising administering to a mammala. therapeutically effective amount of (lS,5S)-3-{5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof. 4 WO 2006/01%60 PCT/US2005/024447 In another embodiment, the present invention relates to pharmaceutical compositions comprising (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0}heptane or a pharmaceutically acceptable salt thereof in combination wiih a pharmaceutically acceptable carrier. 5 In another embodiment, the present invention relates to a pharmaceutical composition for treating pain in a mammal comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, or a pharmaceutically acceptable salt thereof, in combination with a non-steroid anti inflammatory agent 10 In another embodiment, the present invention relates to a pharmaceutical composition for treating pain in a mammal comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt thereof, in combination with an opioid. In another embodiment, the present invention relates to a pharmaceutical composition 15 for treating pain in a mammal comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt thereof, in combination with a tricyclic antidepressant. In another embodiment, the present invention relates to a pharmaceutical composition for treating pain in a mammal comprising administering to a mammal a therapeutically 20 effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt thereof, in combination with an anticonvulsant. In another embodiment, the present invention relates to salts of the (lS,5S)-3-(5,6- dichloro-3-pyridm.yl)-3,6-diazabicyclo[3.2.0]heptane active agent. Specific salts of (1S,5S)- 3-(5,6-dicUoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane contemplated as part of the 25 invention include, for example, acetate, citrate, fumarate, hemicitrate, hydrochloride, maleate, methanesulfonate, 4-methylbenzenesulfonate, sulfate, L-tartrate, and trifluoroacetate.. In another embodiment, the present invention relates to substantially pure salts of the (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane active agent Specific substantially pure salts of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6- 30 diazabicyclo w; contemplated as partof the invention inclaus, for cxcarpls, acetate, citrate, fumarate, hemicitrate, hydrochloride, maleate, methanesulfonate, 4-methylbenzenesulfonate, sulfate, L-tartrate, and trifluoroacetate. 5 WO 2006/019660 PCT/US2005/024447 (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane acetate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 1). Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 5 3,6-diazabicyclo[3.2.0]heptane acetate provided melt / decomposition at 161.0 °C (Figure 1A). The sample size was 2.9550 mg. (1 S,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane hemicitrate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 2). 10 Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane hemicitrate provided melt / decomposition at 169.72 °C (Figure 2A). The sample size was 3.2450 mg. (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane methanesulfonate can be identified by its powder X-ray diffraction pattern in accordance with 15 the Brief Description of the Drawings (Figure 3). Differential scanning calorimetry analysis of (lS)5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane methanesulfonate provided melt / decomposition at 167.23 °C (Figure 3 A). DSC shows that the glass transition temperature is at about 112 °C. The sample size was 3.0600 mg. 20 (lS,5S)-3-(5>6-DicUoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptanemaleatecanbe identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 4). Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane maleate provided melt / decomposition at 162.85 °C (Figure 25 4A). The sample size was 3.7110 mg. (lS,5S)-3-(5,6-Dicchloro-3-idinyl)-3,6-diazabicyclo[3.2.0]heptane hydrochloride can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 5). Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 30 3,6-diazabicyclo[3.2.0]heptane hydrochloride provided meltecomposition at 171.06 °C (Figure 5 A). The sample size was 4.1400 mg. 6 WO 2006/019660 PCT/US2005/024447 (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane i.-tartrate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 6). Characteristic two-theta angles of the powder X-ray diffraction pattern for the tartrate salt were 6.4, 12.6, 13.8, 14.3, 16.5, 17.7, 18.9, 19.2, 22.3, 22.9, 23.5, 5 and 25.0. Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 3,6-diazabicyclo[3.2.0]heptane L-tartrate provided melt / decomposition at 205 °C (Figure 6A). The sample size was 1.640 mg. (lS,5S)-3-(5,6-Dichloro-3 -pyridinyl)-3,6-diazabicyclo[3.2. Ojheptane L-tartrate 10 monohydrate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 6B). Characteristic two-theta angles df the powder X-ray diffraction pattern for the L-tartrate monohydrate salt were 11.19,12.30,14.64,16.81, 17.00, 1S.46, 18.58, 23.07,23.86, 24.75,25.66, and 25.66. The crystallographic unit cell parameters of a single L-tartrate monohydrate crystal have been determined as having the 15 following parameters: a is 31.652(4) A; b is 7.3876(9) A; c is 7.6254(9) A; and p is 91.593(2) A. To afford a cell volume of 1782.4(3) A3, wherein a, b, and c are each a representative length of the crystal lattice and (J is the unique angle. The salt crystallizes in the C2 space group. Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)- 20 3,6-diazabicyclo[3.2.0]heptane L-tartrate monohydrate provided melt / decomposition at 215°C (Figure 6C). The sample size was 3.220 mg. (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane 4-methylbenzenesulfonate (Form H) is solid that can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 7). 25 Characteristic two-theta angles of the powder X-ray diffraction pattern for the 4- ethylbenzenesulfonate (Form H) salt were 8.66,11.48,13.06,16.28,19.87,19.97,20.39, 21.89,23.81,24.79,26.30, and 30.34. The crystallographic unit cell parameters of a single 4- methylbenzenesulfonate (Form IT) crystal have been determined as having the following parameters: a is 9.063(1) A; b is 13.622(2) A; and c is 15.410(2) A. To afford a cell volume 30 of 1902.3(3) A3, wherein a, b, and c are each a representative length of the crystal lathee. The salt crystallizes in the P212121e group. 7 WO 2006/01 %60 PCT/US2005/024447 Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane 4-methylbenzenesulfonate (Form H) provided melt / decomposition at 230°C (Figure 7A). The sample size was 1.310 mg. (1S ,5 S)-3-(5 >6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane 5 4-methylbenzenesulfonate (Form I) is solid that can be identified by its powder X-ray iffraction pattern in accordance with the Brief Description of the Drawings (Figure 7B). Characteristic two-theta angles of the powder X-ray diffraction pattern for the 4- methylbenzenesulfonate (Form I) salt were 8.80, 11.77,13.75,15.12,17.23,18.47, 20.60, 21.82,22.97, 24.73, 26.46,26.60, and 27.42. The crystallographic unit cell parameters of a10 single 4-methylbenzenesulfonate (Form I) crystal have been determined as having the following parameters: a is 8.422(7) A; b is 12.49(1) A; and c is 16.99(1) A. To afford a cell volume of 1788(2) A3, wherein a, b, and c are each a representative length of the crystal lattice. The salt crystallizes in the P2i2i2i space group. (1 S,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane sulfate 15 monohydrate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 8). Characteristic two-theta angles of the powder X-ray diffraction pattern for the sulfate salt were 5.35,13.39,14.18,15.40,16.97,19.15, 21.04, 22.39, 22.66,23.01,23.51, and 24.68. The crystallographic unit cell parameters of a single sulfate salt crystal have been determined as having the following parameters: a is 20 5.6009(6) A; b is 33.017(4) A; c is 6.7495(8) A; and p is 91.419(2) °A. To afford a cell volume of 1247.8(2) A3, wherein a, b, and c are each a representative length of the crystal lattice and p is the unique angle. The salt crystallizes in the P2i space group. (lS,5S)-3-(5,6-DicWoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane sulfate can be identified by its powder X-ray diffraction pattern in accordance with the Brief Description o 25 the Drawings (Figure 8A). Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridhiyl)-3,6-diazabicyclo[3.2.0]heptane sulfate provided melt / decomposition at 215.27°C (Figure 8B). The sample size was 1.190 mg. (lS,5S)-3-(5,6-DicUoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane can be identified 30 by its powder X-ray diffraction pattern in accordance with the Brief Description of the Drawings (Figure 9). Characteristic two-theta angles of the powder X-ray diffraction pattern for (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane were 13.43,18.42, 8 WO 200f,/ PCT/US2005/024447 9.22, 20.06, 21.81, 23.06, 24.37, 24.89, 26.48, 27.30, 27.67, and 32.44. The crystallographic unit cell parameters of a single (lS,5S)-3-(5,6-dicliloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane crystal have been determined as having the following parameters: a is 8.080(3) A; b is 11.159(4) A; and c is 11.903(4) A. To afford a cell volume of 1073.3(6) 5 A , wherein a, b, and c are each a representative length of the crystal lattice. The compound crystallizes in the P2i2i2i space group. Differential scanning calorimetry analysis of (lS,5S)-3-(5,6-dichloro-3-pyridinyi)-3,6-diazabicyclo[3.2.0]heptane provided melt / decomposition at 112 °C (Figure 9A). The sample size was 1.080 mg. 10 As used herein, the term "substantially pure", when used in reference to a (lS,5S)-3- (5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane salt, refers to that salt which is greater than about 90% pure. The crystalline form of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane does not contain more than about 10% of any other compound and, in particular, does not contain more than about 10% of any other form of (lS,5S)-3-(5,6- 15 dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, such as amorphous, solvated forms, non-solvated forms, and desolvated forms. More preferably, the term "substantially pure" refers to a (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane salt which is greater than about 95% pure. In such form, the (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane salt does not contain more than about 5% of any other compound 20 and, in particular, any other form of (1 S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane, such as amorphous, solvated forms, non-solvated forms, and desolvated forms. Even more preferably, the term "substantially pure" refers to a (lS,5S)-3-(5,6-dicUoro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane salt which is greater than about 97% pure. In such salt, the (lS,5S)-3-(5,6-dichloro-3-pyridinyl>3,6- 25 diazabicyclo[3.2.0]heptane salt contains no more than 3% of any other compound and, in particular, does not contain more than 3% of any other form of (1 S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, such as amorphous, solvated forms, non-solvated forms, and desolvated forms. Yet even more preferably, the term "substantially pure" refers to a (lS,5S)-3-(5,6- 30 mcMoro-i-pynamyi)-3,6-uiiu^biCycloi3.2.0]!iept3n5 salt which is greater than about 99% pure. The (lS,5S)-3-(5,6-dicUorcH3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane salt contains no more than about 1% of any other compound and, in particular, any other form of (1S,5S)- 9 WO 2006/019660 PCT/US2005/024447 3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, such as amorphous, solvated forms, non-solvated forms, and desolvated forms. Powder X-ray diffraction (PXRD) analysis of samples was conducted in the following manner. Samples for X-ray diffraction analysis were prepared by spreading the sample 5 powder (ground to a fine powder with mortar and pestle, or with glass microscope slides for limited quantity samples) in a thin layer on the sample holder and gently flattening the sample with a microscope slide. Diffraction patterns were collected using an Inel G3000 diffxactometer equipped with an incident beam germanium monochromator to provide Cu-KQl radiation. The X-ray generator was operated at a voltage of 40 kV and a current of 30 10 mA. The Inel G3000 is equipped with a position sensitive detector that monitors all diffraction data simultaneously. The detector was calibrated by collecting the attenuated direct beam for seven seconds in 1 degree intervals across a 90 degree two theta range. The calibration was checked against a silicon line position reference standard (NIST 640c). Samples were placed on an aluminum sample holder and leveled with a glass slide. 15 S amples were run in one of three configurations: circular bulk holder, a quartz zero background plate or hot stage mount (similar mounting to a zero background plate). Alternatively, X-ray powder diffraction can be performed using a Rigaku Miniflex diffractometer (30 kV and 15 mA; X-ray source: Cu; Range: 2.00-40.00° Two Theta; Scan Rate: 5 degree/minute) or a Scintag XI or X2 diffractometer (2 kW normal focus X-ray tube 20 with either a liquid nitrogen or Peltier cooled germanium solid state detector; 45 kV and 40 mA; X-ray source: Cu; Range: 2.00-40.00° Two Theta; Scan Rate: 1 degree/minute). Characteristic powder X-ray diffraction pattern peak positions are reported for salts in terms of angular positions (two theta) with an allowable variability of ±0.2°. The allowable variability is specified in the U.S. Pharmacopeia, pages 1843-1844 (1995). The variability of 25 ±0.2° is intended to be used when comparing two powder X-ray diffraction patterns. In practice, if a diffraction pattern peak from one pattern is assigned a range of angular positions (two theta) which is the measured peak position ±0.2° and a diffraction pattern peak from another pattern is assigned a range of angular positions (two theta) which is the measured peak position ±0.1° and if those ranges of peak positions overlap, then the two peaks are 30 considered to have the same angular position (two theta). torexampie, ifatiifii'action pattern peak from one pattern is determined to have a peak position of 5.20°, for comparison purposes the allowable variability allows the peak to be assigned a position in the range of 10 WO 2006/019660 l>CT/US2005/024447 5.00°-5.40°. If a comparison peak from the other diffraction pattern is determined to have a peak position of assigned a position in the range of 5.15°-5.55°. Because there is overlap between the two ranges of peak positions (i.e., 5.00°-5.40° and 5.15°-5.55°) the two peaks being compared are considered to have the same angular position (two theta). 5 Single Crystal X-ray diffraction analysis of samples was conducted in the following manner. Samples for X-ray diffraction analysis were prepared by affixing selected single crystals to glass pins with epoxy adhesive. X-ray diffraction data was collected using a Bruker SMART system with an APEX area detector (50 kV and 40 mA; X-ray source: Mo). Data were collected at -90 °C. 10 It is understood that (iS,5S)-3-(5,6-dichloropyridin-3-yl)-3,6- diazabicyclo[3.2.0]heptane and salts thereof can be identified by characteristic peaks in their powder X-ray diffraction pattern. One with skill in the art in analytical chemistry would be able to readily identify (lS,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane or a salt of (lS,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane by as few as 15 one characteristic peak in the powder X-ray diffraction pattern. Differential scanning calorimetric (DSC) analysis of samples was conducted in the following manner. A.T.A. Instruments Model Q1000 differential scanning calorimeter with a Mettler 821 DSC cell using standard software to identify the onset of the melt. The analysis parameters were: sample weight 1-3 mg, placed in an aluminum pan, and sealed after a pin 20 hole was poked in the lid; heating rate: 10 ° CVniinute). One method for preparing (15,55)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane is shown below in Scheme 1. Scheme 1 25 11 WO 2006/019660 PCT/US2005/024447 As shown in Scheme 1, the sequential treatment of 2-hydroxy-5-nitropyriduie with 5 potassium chlorate under heated conditions provides 3-chloro-2-hydroxy-5-nitropyridine which when further treated with phosphorous oxychloride under heated conditions provides 2)3-dichloro-5-nitropyridine. The nitro containing compound when treated to the reductive conditions of Raney-nickel and 40 PSI of hydrogen provides the amine which when further treated with glyoxal-l,2-dimethyl acetal in the presence of Raney-nickel under heated 10 condition provides (5,6-dicUoro-pyrid^-3-yl)-(2,2-dimemoxy-emyi)-amine. The amine when treated with allyl bromide and methyl tributyl ammonium chloride in a mixture of methyl tert-butyl ether and 50% aqueous sodium hydroxide provides allyl-(5,6-dichloro-pyridm-3-yl)-(2,2-dimemoxy-emyl)amine (Compound 5D). The synthesis cf compound cf formula A wherein the phenyl group may be optionally 15 substituted with groups such as alkyl, alkoxy or halo may be achieved according to the following pathway. (S)-phenylglycinol (or a substituted version) when treated with p- 12 WO 2006/019660 l'CT/l)S2005/0 24447 anisaldehydc in methyl lert-butyl ether under reflux condition under a Dean-Stark trap followed by cooling to 0 "C, diluting with a solvent such as tetrahydrofuran and treating with m-chloroperoxybenzoic acid and hydroxylamine provides compounds of formula A. The treatment of Compound 5D with an acid such as hydrochloric acid under cooling 5 conditions provides (allyl-5,6-dichloro-pyridin-3-yl)-amino)-acetaldehyde which when reated with 2-(S)-hydroxyamino-2-phenyl-ethanol and magnesium bromide in a solvent such as isopropyl alcohol provides (3S,4S)-2-[5-(5,6-dichloro-pyridin-3-yl)-hexahydro- pyrrolo[3,4-c]isoxazol-l-yl]-2-(2'S)-phenyl-ethanol (Compound 5G). Compound 5G when treated with methanesulfonyl chloride to generate the mesylate which is then treated with 10 sodium tert-butoxide followed by an acidic workup provides (3S, 4S)-5-(5,6-dichloro- yridin-3-yl)-hexahydro-pyrrolo[3,4-c)isoxazole (Compound 5H). The treatment of Compound 5H with Raney-nickel and 40 PSI of hydrogen in a mixture of tetrahydrofuran, ethanol and water provides (3S, 4S)-[4-arrimo-l-(5,6-dichloro-pyridin-3-yl)-pyrrolidin-3-yl]- methanol (Compound 51). The treatment of Compound 51 with thionyl chloride and N- 15 methylpyrrolidinone under heated conditions in 1,2-dimethoxyethane followed by treatment with sodium hydroxide or another similar base provides (IS, 5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane (Compound 51). Hydroxyl groups described in the processes may be converted into a leaving group when necessary during me synthesis of other described compounds or as needed according to 20 one skilled in the art to assist conversion into another functional group. Some of the methods contemplated include but are not limited to the treatment of alcohols with reagents such as methane sulfonyl chloride, trifluoromethane sulfonyl chloride, p-toluenesulfonyl chloride, thionyl chloride, methane sulfonyl anhydride, trifluoromemane sulfonyl anhydride. These transformation may be carried out in the presence of a base in a solvent such as but. Not 25 limited to tetrahydrofuran or dichloromethane. Typical bases useful for these transformation include but are not limited to triethylamine, N-methylmorpholine, ethyl diisopropylamine and those known to one skilled in the art. An alternative process for preparing (15',5iS)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane is described in the Examples below. The Examples are intended 30 as a illustration of the compounds and methods of the invention and not intended to limit the scope of the invention, which is defined by the appended claims. 13 WO 2006/01 %60 PCT/US2005/024447 EXAMPLES Preparation of (l.y,5.y)-3-(5.6-Dichloro-3-pvridinvl)3,6-diazabicvclor3.2.01heptane 5 Example 1 tert-Butyl(lJ^,5iS^-3,6-diazabicvclof3.2.0]heptane-6-carboxvlate Example 1A Benzyl 2,2-dimethoxvemylcarbamate 10 Benzyl chloroforrnate (231.3 g, 1.3 mol) was added gradually to a mixture of minoacetaldehyde dimethyl acetal (152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20°C. After the addition was completed, the mixture was stirred at ambient temperature about 4 hours. The organic layer was separated, washed with brine (2 x 100 mL) and concentrated to provide the title compound. 15 *H NMR (CDC13, 300 MHz) 8 3.33 (t, J=6.0Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCI/NH3) m/z 257 (M+NH4)+ (M+H)+. Example IB Benzyl ally(2.2-dimemoxvethyl')carbamate 20 The product of Example 1A (281.0 g, 1.18 mol) in dry toluene (1.0 L) was treated with powdered KOH (291.2 g, 5.20 mol) and triethylbenzylammonium chloride (4.4 g, 0.02 mol). A solution of allyl bromide (188.7 g, 1.56 mol) in toluene (300 mL) was then added dropwise over 1 hour at 20-30 °C. The mixture was stirred overnight at room temperature and then water (300 mL) was added over 20 minutes at 20-30 °C. The layers were separated 25 and the aqueous phase was extracted with toluene ( 2 x 300 mL). The organic phases were combined, washed with brine (2 x 100 mL), dried (K.2CO3), filtered and the filtrate concentrated to provide the title compound. lH NMR (MeOH-d4,300 MHz) 8 3.32 (s, 3H) 3.37 (m, 5H), 3.97 (d, J=5.4 Hz, 2H), 4.40-4.50 (m, 1H), 5.15 (m, 4H), 5.75 (m, 1H), 7.23 (m, 5H); MS (DCI/NH3) m/z 297 (M+NH4)+, 280 (M+H)+. 30 Example 1C Benzyl allyl(2-oxoethyl)carbamate 14 WO 2(HK./05/024447 The product of Example IB (314.0 g, 1.125 mol) was treated with formic acid (88%, 350 mL) at room temperature and allowed to stir for 15 hours. Most of the formic acid was removed by concentration under reduced pressure at 40-50°C. The residue was extracted with ethyl acetate (3 x 500 mL). The extracts were combined and washed with brine until the 5 wash had a pH = 6-7. The organic phase was concentrated to provide the title compound. *H NMR (CDC13,300 MHz) 5 3.20 (m, IH), 3.97 (m, 2H), 4.10 (m, IH), 5.10 (m, 4H), 5.75 (m, IH), 7.45 (m, 5H), 9.50 (d, J=6.4 Hz, IH); MS (DCI/NH3) m/z 234 (M+H)+. Example ID 10 Benzyl allyl[2-(hydroxyimino)ethyl]carbamate The product of Example 1C (260 g, 1.115 mol) in acetonitrile (1.5 L) was treated with sodium acetate trihydrate (170.6 g, 4.41 mol) in distilled water (750 mL) and NH2OH hydrochloride (98.0 g, 4.41 mol) under N2. The mixture was stirred at room temperature for about 20 hours. The volatiles were removed under reduced pressure and the residue was 15 extracted with ethyl acetate (2 x 750 mL). The combined organic phases were washed with brine until the wash had a pH = 7. The organic phase was concentrated to provide the title compound. *H NMR (MeOH-d,, 300 MHz) 5 3.94 (m, 2H), 3.98 (d, J=5.5Hz, IH), 4.17 (d, J=4.4 Hz, IH), 5.30 (m, 4H), 5.60 (m, IH), 7.40 (m, 5H). MS (DCI/NH3) m/z 266M+NH4)+, 249 (M+H)+. 20 Example IE Benzyl cis-3-amino-4-(hydroxymethyl)-1-pyrrolidinecarboxylate A solution of the product of Example 1D(240g,0.97mol)in 30 approximately 200 mL. This residue was basified to pH 9-10 by addition of saturat aqueous Na2C03- The precipitated white solid was removed by filtration and the filtrate was extracted with CHCI3 (3 x 600 mL). The combined organic phases were washed with 15 WO 2006/019660 PCT/US2005/024447 saturated Na2C03 solution (2 x 50 mL) and dried over anhydrous Na2CC>3. The mixture was filtered through a short column of diatomaceous earth and the filtrate was concentrated to provide the title compound. 'H NMR (MeOH-d4, 300 MHz) 5 2.40 (m, 1H), 3.30 (m, 2H), 3.80-3.50 (m, 5H), 5.10 (s, 2H), 7.35 (m, 5H); MS (DCI/NH3) m/z 251 (M+H)+. 5 Alternatively, the product of Example IB (75.3 Kg) in toluene solution (364.6 kg) was charged to a 200-gallon glass reactor, and the toluene was removed by distillation. The distillation, performed under vacuum and at an internal temperature of not more than 70 °C, was judged to be complete when the toluene content was less than 40wt%. The contents of 10 the reactor were cooled to 23 °C and formic acid (172 Kg) was added, followed by water (15.1 Kg). The contents of the reactor were stirred at room temperature until there was less than 1% starting material remaining. The contents of the reactor were cooled to 5 °C, and 50% NH2OH aqueous solution (34.5 Kg) was charged slowly to the reactor over 45 min. The contents of the reactor were stirred at room temperature until there was less than lwt% 15 intermediate 1C remaining. Water (292 Kg) was charged to the reactor, followed by addition of n-pentanol (148 Kg). The contents of the reactor were stirred for 15 min. The layers were separated and the bottom aqueous layer was extracted again with n-pentanol (148 kg). The n-pentanol layers containing intermediate ID were combined and cooled to 5 °C. The pH of the n-pentanol layer was adjusted to 8.5 with 25% NaOH solution (244 Kg), mamtaining the 20 internal temperature at not more than 35 °C. The layers were separated, and the n-pentanol layer was washed with 25% NaCl solution (262 Kg). The organic layer was collected and vacuum distilled, at a temperature less than 85 °C, to remove any remaining toluene carried over from step 2. More n-pentanol was added back as necessary, so that the final concentration of 4 was 20-30wt%. Distillation was continued until the level of toluene was 25 less than 2 wt% and the water content was less than 0.2 wt%. The solution assay yield of intermediate ID was determined to be 63.5 Kg (97%). The intermediate ID was not isolated, and the solution was charged to a 200-gallon glass-lined reactor, equipped with a mechanical agitator, condenser, temperature probe and nitrogen inlet and diluted with n-pentanol to give ~10%wt solution. The contents of the reactor was heated to NLT 133°C, 30 target 135°C, for 13 hours. Thereaction was cooled to room tenipsrature and then transferred to tared poly-lined drums. The solution assay yield was determined to be 54.8 Kg (86%). Raney Nickel (6.2 Kg, 25wt%), ethanol (50 Kg) and about half of this solution (298 16 WO 2IMI6/019660 PCT/US2005/024447 Kg solution, 24.5 Kg by assay) were charged to a reactor. The internal temperature of the reactor was adjusted to 25 ± 5°C. The reactor was then pressure purged with hydrogen 3 times. The solution was hydrogenated at NMT 60 psig, target 40 psig, for NLT 4 hours while maintaining an internal temperature of 25 ± 15°C. Upon completion of the reaction the 5 contents of the reactor were filtered through filter aid to remove the catalyst and the Step 6 product solution was collected in poly-lined drums. The total solution assay yield was determined to be 21.6 Kg (96%). The product IE was not isolated, and was taken on to the next step as a solution. 10 Example IF Benzyl (4aS,7aS)-2,2-dimethylhexahydropyrrolo[3,4-d][1,3]oxazine-6(4H)-carboxylate (R)-mandelate product of Example IE (140g, 0.56 mol) in dry acetone (150 mL ) was treated with 2-methoxypropene (55 mL, 0.57 mol) at room temperature overnight. The reaction 15 mixture was concentrated under reduced pressure and the residue was dissolved in dry cetone (750 mL). ©-Mandelic acid (85 g, 0.56 mol) was added and the solution was stirred at room temperature for 48 hours. The precipitate was isolated by filtration and dried under reduced pressure to provide the title compound as a solid. lH NMR (MeOH-d4,300 MHz) 8 1.20-1.40 (m, 3H), 2.09 (s, 3H), 3.30 (m, IH), 3.48-3.75 (m, 6H), 4.20 (m, IH), 5.10 (m, 3H 20 7.25-7.52 (m, 10H); MS (DCI/NH3) m/z 291 (M+H)+. Example 1G Benzyl (3S,4S)-3-[(tert-butoxycarbonyl)amino]-4-(hydroxymethyl)-1-pyrrolidinecarboxylate(S)-mandelate 25 The product of Example IE n-pentanol/ethanol was charged to a glass-lined reactor, quipped with a mechanical agitator, condenser, temperature probe and nitrogen inlet The contents of the reactor were distilled under vacuum with a jacket temperature of NMT 85°C to a volume of 400 L is to remove both the water and the ethanol. The internal temperature was then adjusted to 25°C. The mixture was diluted with n-pentanol to -10% wt IE then (5) 30 mandelic acid (17.0 Kg) was charged. The internal temperature of the reactor was adjusted to 75°C to dissolve all the solids. The internal temperature was then adjusted to 60°C, at which point seed crystals (250 g) were added to the reactor. The contents of the reactor were stirred 17 WO 2006/01966(1 PCT/US2005/024447 t an internal temperature of 60 ± 5°C for not less than 3 hours. The internal temperature of the reactor was lowered to 25°C at a rate of 5°C per hour, and then the contents of the reactor were stirred at 25°C for not less than 6 hours. The contents of the reactor were filtered, and the wetcake was washed with n-pentanol (50 Kg). After the wetcake was blown dry with 5 nitrogen for at least 4 hours, the product was dried for at least 24 hours in a hastelloy tray dryer under vacuum at 55°C, with a nitrogen bleed. A total of 27.7 Kg 18 was obtained (38%), with > 99 % purity and 96% diastereomeric excess. Example 1H 10 Benzyl (35',4.S)-3-[(tert-butoxyarbony)ammol-4-(rivdroxvmemvl)-pvrrolidinecarboxvlate The product of Example IF (56 g, 127 mmoi) in ethanol (50 mL) was treated with 5% aqueous H2SO4 (100 mL) at room temperature and allowed to stir for 16 hours. The mixture was basified to pH -10 with 20% aqueous NaOH (50 mL) and then the mixture was treated with di-tert-butyl dicarbonate (41.5 g, 190 mmol) in ethanol (50 mL) at 10-20 °C. After 15 stirring at room temperature for 4 hours, the ethanol was removed under reduced pressure and the residue was extracted with ethyl acetate (3 x 500 mL). The combined organic phases were washed with brine (2 x 100 mL) and concentrated to provide the title compound. The enantiopurity of the title compound was determined to be greater than or equal 99% enantiomeric excess by HPLC (HPLC conditions: Chiracel AD column; 20 ethanol/hexanes=20/80, flow rate, 1.0 mL/minute20 nm; retention time 10.8 minutes). *H NMR (MeOH-d4,300 MHz) δ 1.46 (s, 9H), 2.50 (m, 1H), 3.25 (m, 1H), 3.40 (m, 1H), 3.50-3.75 (m, 4H), 4.20 (m, 1H), 5.10 (s, 2H), 7.35 (m, 5H); MS (DCI/NH3) m/z 368 (M+N&O*, 351 (M+H)+. Alternatively, the product of Example 1G (13.3 Kg) was charged to a glass-lined 25 reactor with ethyl acetate (89.9 Kg) and the internal temperature adjusted to 25 °C. To this slurry was charged a 50 wt% solution of aqueous potassium carbonate (73 Kg). To the stirred suspension was charged a solution of di-f-butyldicarbonate (9.4 Kg) in ethyl acetate (44.2 Kg). The reaction mixture was stirred at 25 °C until complete. The reaction mixture was quenched withN,Nmylemylenediamme (0.55 Kg), followed by the addition of 30 ethyl acetate (85.8 Kg) and water (66 Kg). After separating the layers, the organic layer was washed with a solution of potassium phosphate buffer (28.4 kg). The buffer solution was made using 13.3g potassium phosphate monobasic and 50.8 g potassium phosphate dibasic 18 WO 2006/0t'K.f.O PCT/US2O05/024447 er kilogram of water. The wash was repeated until the pH of the aqueous solution after the wash was less than 8.0. The organic layer was washed with a 20 wt% solution of sodium chloride (75 kg) and was assayed by HPLC to contain 4.5 wt% intermediate 1H, corresponding to 10.23 Kg (88%). The ethyl acetate solution was distilled under vacuum. 5 The product slurry was used immediately in the next step. Example II Benzyl (3S,4S)-3-[(tert-butoxcarbonyl)amino]-4-{[(methylsulfonyl)oxy]methyl}-1- pyrrolidinecarboxylate he product of Example 1H (43.7 g, 125 mmol) and triethylamine (25.2 g, 250 mmol) n CH2CI2 (600 mL) were treated with methanesulfonyl chloride (12.6 mL, 163 mmol) over 30 minutes at -10 °C. The solution was allowed to warm to room temperature over 1 hour and quenched with water (100 mL). The layers were separated and the aqueous phase was extracted with CH2C12 (2 x 400 mL). The combined organic phases were washed with brine 15 (2 x 100 mL), dried over Na2S04, filtered, and the filtrate concentrated to provide the title compound. lH NMR (CDC13,300 MHz) 8 1.46 (s, 9H), 2.80 (m, 1H), 3.08 (s, 3H), 3.40(m, 2H), 3.70 (m, 2H), 4.10 (m, 1H), 4.40 (m, 2H), 4.75 (m, 1H), 5.16 (s, 2H), 7.30 m, 5H); MS (DCI/NH3) m/z 446 (M+NH4)+, 429 (M+H)20 Example 1J Benzyl (3S,4S)-3-amino-4-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylate trifluroacetate he product of Example II (43.7 g, 125 mmol) in CH2C12 (150 mL) was treated with trifluoroacetic acid (50 mL) at room temperature and allowed to stir for 1 hour. The mixture 25 was concentrated under reduced pressure to give the title compound. *H NMR (CDCI3,300 MHz) 5 2.80 (m, 1H), 3.15 (s, 3H), 3.40(m, 1H), 3.70 (m, 3H), 4.10 (m, 1H), 4.05 (m, 1H), 4.44 (m, 2H), 5.16 (s, 2H), 7.30-7.50(m, 5H); MS (DCI/NH3) m/z 329 (M+H)Example IK 30 Benzyl (lS,5S)-3,6-dizabicyclo[3.2.0]heptane-3-carboxylate The product of Example 1J was dissolved in ethanol (250 mL) and basified to pH ~12 with 25% aqueous NaOH. The mixture was warmed to 60 °C for 1.5 hours. The reaction wo 2006/01 mo PCT/US2005/024447 mixture was allowed to cool to room temperature and used in the next step without further purification. An analytical sample was removed (~lmL) and concentrated under reduced pressure. The residue was extracted with CHCI3 (2x5 mL). The extracts were combined, washed with brine (3x2 mL) and then passed through a short column of diatomaceous earth. 5 The filtrate was concentrated to provide an analytical amount of the title compound. H NMR (MeOH-d4, 300 MHz) 5 3.30-3.16 (m, 3H), 3.36 (m, IH), 3.82 (m, 3H), 4.55 (m, IH), 5.20 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 250 (M+NKUV, 233 (M+H)+. Example 1L 10 3-Benzvl, 6-tert-butvl-(lJ?,5y)-3,6-diazabicvclo[3.2.01heptane-3.6-dicarboxvlate The solution of Example IK was slowly added to di-tert-butyl dicarbonate (40.9 g, 188 mmol) in ethanol (50 mL) over 30 rninutes at room temperature. The mixture was stirred at room temperature for additional 0.5-1 hours. The reaction mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (3 x 500 mL). The ethyl 15 acetate extracts were combined, washed with brine (3 x 50 mL), stirred with KHSO4 (5%, 100 mL) for 10 minutes and the phases separated. The organic layer was washed with brine (3 x 50 mL) and passed through a short column of diatomaceous earth. The filtrate was concentrated to provide the title compound which was used in the next step without further purification. lH NMR (MeOH-d,, 300 MHz) 6 1.4 (s, 9H), 3.10 (m, 2H), 3.30 (m, IH), 3.45 20 (m, IH), 3.90 (d, J=12.2 Hz, IH), 4.06 (m, 2H), 4.66 (dd, J=6.4,2.0 Hz, IH), 5.16 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 333 (M+H)+. Example 1M tert-Butyl(1R,5S)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate 25 The product of Example 1L (40.0 g, 0.120 mol) was dissolved in methanol (400 mL) and treated with Pd/C (10 wt%, 4.0g) under H2 at room temperature for 10 hours. The reaction mixture was filtered through auhort column of diatomaceous earth and the filtrate was concentrated to provide the title compound. lH NMR (MeOH-d^ 300 MHz) 5 1.43 (s, 9H), 2.47(dd, J=12.6,3.8 Hz, IH), 2.62 (dd, J=12.2,5.7 Hz, IH), 2.96 (m, IH), 3.05 (d, 30 J=12.2 Hz, IH), 3.22 (d, J=12.5 Hz, IH), 3.45 (iii, III), 3.95 (m, IH), 4.63 (dd, J=6.1,3.7 Hz, IH); MS (DCI/NH3) m/z 199 (M+H)+. 20 WO 2006/019660 PCT/US2005/024447 Example 2 5-Bromo-2,3-dichloropyridine Example 2A 5 3-Chloro-5-nitro-2-pyridinol A 5L flask with mechanical stirrer, thermocouple, and addition funnel was charged with 2-hydroxy-5-nitropyridine (200 g,) and concentrated HCl (890 mL). The mixture was warmed to 50 - 55 °C and a solution of KCIO3 (61.3 g, 0.5 mol) in water (850 mL) was added dropwise over 75 minutes maintaining the reaction temperature at 55 - 59 °C. Following 10 complete addition, the reaction mixture was cooled in an ice-water bath to an internal temperature of <6 °C and then filtered. The filter cake was washed with cold water (700 mL) and dried under vacuum at 50 °C for 12 hours to provide the title compound. *H NMR (CDCI3, 300 MHz) 5 7.43 (d, J=3 Hz, 1H), 7.59 (d, J=3 Hz, 1H). 15 Example 2B 2t3-Dichloro-5-nitropvriduie A 2L flask with mechanical stirrer and thermocouple was charged with POCI3 (200 g, 1.30 mol). The flask was cooled in an ice bath to an internal temperature of 0-5 °C as quinoline (84 g, 0.65 mol) was added. The product of Example 2A (227 g, 1.30 mol) was 20 added in portions, so as to maintain the reaction temperature below 10 °C. The cold bath was removed, and the mixture was warmed to 120 °C for 90 minutes. The temperature was decreased to 100 °C and the reaction mixture was quenched by addition of water (500 mL) mainining the internal temperature between 100-110 °C. After complete addition, the mixture was cooled in ice to 0-5 °C for 1 hour and filtered. The filter cake was washed with 25 cold water and dried under vacuum at 40 °C to provide the title compound. *H NMR (CDCI3, 300 MHz) 5 8.39 (d, J=3 Hz, 1H), 9.16 (d, J=3 Hz, 1H). Example 2C 5-Amino-23-dichloropvridine 30 Anhydious SnCl2(2C'J g, 1.58=molnd ccrrenirKtodHCl (350 mL) were charged to a 5L flask with mechanical stirrer and thermocouple. The flask was cooled in ice and the product of Example 2B (100 g, 0.518 mol) was added in portions maintaining the temperature 21 WO 2006/01<>660 PCT/US2005/024447 elow 65 °C. After the addition was complete, the cold bath was removed, and the mixture was stirred for 2 hours at ambient temperature. The mixture was cooled in ice as 25% aqueous NaOH (1000 mL) was added to bring the mixture to pH >10. The mixture was extracted with CH2C12 (1 x 600 mL, 2 x 400 mL) and the combined extracts were washed 5 with brine (200 mL), dried (MgSO/t), and concentrated under vacuum. The residual solid was crystallized from a mixture of water (500 mL) and ethanol (100 mL) to provide the title compound as a solid. !H NMR (CDC13, 300 MHz) 5 3.80 (br s, 2H), 7.10 (d, J=3 Hz, 1H), 7.77 (d, J=3 Hz, 1H); MS (DCI/NH3) m/z 180/182/184 (M+NrL/ 163/165/167 (M+H)+. 10 Example 2D 5-Bromo-2,3-dichloropyridine A 5L flask with mechanical stirrer, thermocouple, and addition funnel was charged with the product of Example 2C (70 g, 429 mmol) and 48% HBraq (240 mL). The suspension was maintained at 0-5 °C as a solution of NaNC>2 (32.0g, 464 mmol) in water (100 mL) was 15 added dropwise over 1 hour. Additional water (200 mL) was added and the mixture was stirred for 10 minutes at 0-5 °C. The mixture was treated with CuBr (32.6 g, 227 mmol) in portions over 20 minutes followed by additional water to maintain a fluid reaction mixture. The mixture was allowed to warm to room temperature and diluted with water. The mixture was distilled at ambient pressure, until the distillate ran clear (1.5 L collected). The distillate 20 was extracted with EtOAc (3 X 500 mL) and the combined extracts were washed with brine (100 mL), dried (MgSO), and concentrated to provide 5-bromo-2,3-dichloropyridine as a solid. *H NMR (CDCU, 300 MHz) 8 7.94 (d, J=3 Hz, 1H), 8.38 (d, J=3 Hz, 1H). Example 3 25 (1S,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane (L)-tartrate Example 3A tert-Butyl(1R,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate 30 AIL flask with mechanical stirrer was charged with a solution of ten-butyi (iR.5S)- 3,6-diazabicyclo[3.2.0]heptane-6-carboxylate (10.0 g, 50 mmol, product of Example 1L) and 5-bromo-2,3-dichloropyridine (14.0 g, from Example 2D) in toluene (400 mL). The flask 22 WO 2006/019660 PCT/US2005/024447 was evacuated and purged three times with nitrogen. Xantphos (1.74 g, 3 mmol), Pd2(dba)3 (916 mg, 1 mmol) and sodium tert-butoxidc (7.20 g, 75 mmol) were added successively to the flask against a purge of nitrogen gas. The flask was again evacuated and purged with nitrogen (3 times) and the mixture heated to 85-90 °C under N2. After 2 hours, the reaction 5 was cooled to room temperature, diluted with ethyl acetate (1000 mL) and water (200 mL), and stirred for 5 minutes. The organic phase was separated, washed with brine (200 mL), dried (MgS04), filtered through Celite® (diatomaceous earth) and the filtrate concentrated under vacuum to provide the title compound which was used in the next step without further purification. 'H NMR (MeOH-d4, 300 MHz) 8 1.45 (s, 9H), 2.94 (dd, J=11.6, 4.4 Hz, 1H), 10 3.04 (dd, J=10.2, 6.4 Hz, 1H), 3.3 (m, 1H), 3.58 (m, 1H), 3.78 (d, J=10.5 Hz, 1H), 3.90 (d, J=10.8 Hz, 1H), 4.05 (m, 1H), 4.83 (m, 1H) 7.39 (d, J=2.7 Hz, 1H), 7.84 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 344/346/348 (M+H)+. Example 3B 15 (1S,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane p-toluenesulfonate he product of Example 3 A (23.2 g) was dissolved in ethyl acetate (250 mL) and p- toluenesulfonic acid monohydrate (11.4 g, 60 mmol) was added. The solution was wanned to reflux and stirred for 90 minutes, cooled to room temperature, and allowed to stand for 12 20 hours to complete precipitation. The solid was isolated by filtration and dried to provide the itle compound, mp 174-178 °C; [a]D20=-20.0°(MeOH, 0.105); !H NMR (MeOH-d,, 300 MHz) 5 2.36 (s, 3H), 3.06 (dd, J=10.5,6.1 Hz, 1H), 3.17 (dd, J=12.2,4.8 Hz, 1H), 3.50 (m, 1H), 3.72 (dd, J=11.2,5.4 Hz, 1H), 3.90 (d, J=10.5 Hz, 1H), 4.10 (d, J=12.6.Hz, 1H), 4.25 (dd, J=11.2,9.8 Hz, 1H), 5.05 (dd, J=6.7,5.1 Hz, 1H) 7.22 (d, J=8.l Hz, 2H), 7.52 (d, J=2.7 25 Hz, 1H), 7.69 (d, J=8.1 Hz, 2H), 7.95 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 244/2467248 (M+H)+. Example 3C (1S,5S)-3-(5,6-Dichloropyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane 30 The product of Example 3B (33 g, 79 niniol) was stirred in 330 mL ot 5 NaOHin water for 10 minutes and extracted with CHCl3:i-PrOH (10:1) (4 x 500 mL). The extracts were combined, washed with brine (2 x 100 mL), and concentrated to give the title compound 23 WO 2006/019660 PCT/US2005/024447 as a solid. lH NMR (MeOII-d4, 300 MHz) δ 3.04 (dd, J=10.9, 4.8 Hz, 1H), 3.11 (dd, J=10.2, 6.8 Hz, 1H), 3.26 (dd, J=8.8,4.4 Hz, 1H), 3.38 (m, 1H), 3.73 (t, J=l 1.2 Hz, 2H), 3.84 (t, J=8.1 Hz, HI), 4.55 (dd, J=6.8, 4.8 Hz, 1H), 7.37 (d, J=3.1 Hz, 1H), 7.84 (d, J=2.7 Hz, 1H); MS (DCI/NHj) m/z 244/246/248 (M+H)+. 5 Example 3D (1S,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane (L)-tartrate he product from Example 3C (12.0 g, 50 mmol) in MeOH (400 mL) was heated to 10 65 °C and treated with (L)-tartaric acid (9.0 g, 60 mmol) in MeOH (60 mL) dropwise. After omplete addition, the mixture was stirred at reflux for 2 hours and then allowed to cool to room temperature. After stirring at room temperature for 10 hours, the mixture was filtered and the filter cake washed with chilled methanol (10 mL). The solid was dried under vacuum to provide the title compound, mp 210-212 °C (decomp); [a]D20 = -27.02° (MeOH, 0.105); 15 1 NMR (MeOH-d4, 300 MHz) 6 3.12 (dd, J=10.9,6.1 Hz, 1H), 3.22 (dd, J=12.9, 5.1 Hz, 1H), 3.54 (m, 1H), 3.76 (dd, J=11.6, 5.1 Hz, 1H), 3.87 (d, J=10.9 Hz, 1H), 4.10 (d, J=12.6 Hz, 1H), 4.31 (dd, J=l 1.2, 8.5 Hz, 1H), 4.77 (s, 2H), 5.13 (dd, J=7.2, 5.1 Hz, 1H) 7.54 (d, J=2.7 Hz, 1H), 7.90 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 244/246/248 (M+H)+- 20 Example 4 The product from Example 3C (10.0 g) was partitioned between methylene chloride (200 mL) and 20% aqueous potassium hydroxide (150 mL). The layers were separated, and the organic layer was washed with more 20% aqueous potassium hydroxide (2 x 150 mL). 25 The organic layer was then washed with saturated brine solution (100 mL). This was concentrated to an oily solid, and then dissolved up in isopropyl acetate. Upon concentration by distillation to ~50 mL, solids started to crystallize. More isopropyl acetate (200 mL) was added and this was concentrated to -25 mL. After cooling in an ice bam, the resulting solids were filtered and die weloake was washed with isoprcpyi acetate. The product was dried in 30 the vacuum oven at 50 °C to give a solid. lH NMR (CDC13,400 MHZ) 8 3.04 (dd, J = 11, 8 Hz, 1H), 3.15 (dd, J = 10,7 Hz, 1H), 3.30-3.38 (m, 2H), 3.6 (d, J = 11 Hz, 1H), 3.88 (d, J = 24 WO UMtMWMM l,CT/US2005/024447 10 Hz, IH), 3.91 (t, J = 8 Hz, 1H), 4.60 (m, 1H), 7.07 (d, J = 3 Hz,lH), 7.75 (d, J = 3 Hz, 1H). Example 5 5 (IS, 5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane Example 5A 3-Chloro-2-hydroxy-5-nitropyridine Concentrated hydrocliloric acid (239 g) was added to 2-hydroxy-5-nitropyridine (40.0 10 g). The resulting slurry was heated to 53 °C, and stirred until all the solids dissolved. To this was slowly added a solution of potassium chlorate (14.0 g) in water (250 g), while maintaining the temperature between 55 °C and 59 °C. The resulting mixture was stirred at 58-62 °C for about 1 hour. The reaction was then cooled to room temperature, stirred for 12 hours and then filtered. After washing the wet cake with water, the product was dried in a 15 vacuum oven. !H NMR (400 MHz/DMSO-d6) 5 8.64 (d, /= 2.9 Hz, IH), 8.35 (d, J= 2.9 Hz,lH) Example 5B 23-Dichloro-5-nitropyridine (Compound 5B) 20 A mixture of 3-chloro-2-hydroxy-5-nitropyridine (36.0 g), acetonitrile (72 mL), and phosphorus oxychloride (37.5 g) was heated to 80 °C. The reaction was then stirred at this temperature for about 15 hours. After cooling the reaction to 40 °C, water (27 g) was added, while maintaining the temperature below 70 °C. The temperature was adjusted to 45 °C, and then more water (189 g) was added slowly. The reaction was then cooled to 23 °C, stirred for 25 at least 12 hours, and then filtered. After washing the wet cake with water, the product was dried in a vacuum oven. *H NMR (400 MHz/CDCl3) 5 9.10 (d, J= 2.5 Hz, IH), 8.56 (d, /= 2.4 Hz, IH) Example 5C 30 (5,6-Dichloro-pyridin-3 –yl-(2.2-dimemoxy-emyl)-arnine To a Parr bottle was charged Raney Nickel (10.1 g), water (40.0 g), tetrahydromran (166.3 g), ethanol (32.0 g) and acetic acid (2.5 g). A solution of 2,3-dichloro-5-nitropyridme 25 WO 2006/019660 PCT/US2005/024447 (40.0 g) in tetrahydrofuran (40.1 g) was added to the Parr bottle in four portions and the mixture was hydrogenated at 40 psi and 35 °C for about 1 hour after each addition. The reaction mixture was cooled to room temperature, and then glyoxal-l,2-dimethyl acetal (47.2 g of 50 wt% aqueous), tetrahydrofuran (35.6 g) and water (80.4 g) were added and the 5 mixture was hydrogenated at 40 psi and 50 °C for about 12 hours. The reaction was cooled to room temperature and then filtered through a bed of Hy-Flo. The pH of the filtrate was adjusted to 7 with 5% aqueous phosphoric acid, and then the mixture was concentrated. Isopropyl acetate (79 g) was added, this was concentrated, and then more isopropyl acetate (485 g) was added. After warming to 50 °C to dissolve the solids, the solution was washed 10 with 5% aqueous phosphoric acid (3 x 215 g) and then washed with 20% aqueous sodium chloride solution (231 g). The organic solution was concentrated to about 78 mL and heptane (124 g) was added. After heating to 83 °C to dissolve everything, the solution was slowly cooled to room temperature. More heptane (124 g) was added and then the suspension was cooled to 5 °C. After filtering, the wetcake was washed with cold heptane/isopropyl acetate 15 and then dried in the vacuum oven. lH NMR (400 MHz/CDCl3) 8 7.71 (d, J= 2.7 Hz, 1H), 7.01 (d, J= 2.7 Hz, 1H), 4.53 (t, J= 5.2 Hz, 1H),4.05 (s, br, 1H), 3.42 (s, 6H), 3.22 (d, /= 5.21 Hz, 2H). Example 5D 20 Allyl-(5,6-dichloro-pyridin-3-yl)-(2,2-dimemoxy-ethyl-amine (Compound 5D) To a mixture of (5,6^ichloro-pyridin-3-yl)-(2,2-dimethoxy-emyl)-amine (190 g), allyl bromide (137.4 g), and methyl tributyl ammonium chloride (23.8 g) in methyl tert-butyl ether (1140mL) was added 50% aqueous sodium hydroxide (665 mL). This was then stirred at 25-35 °C for about 24 hours. Then water (375 g) and methyl tert-butyl ether (280 g) were 25 added and then the layers were separated. The organic layer was washed with l0mM potassium phosphate dibasic/l0mM potassium phosphate monobasic aqueous solution (3 x 1 000mL), and then washed with 20% aqueous sodium chloride (l000mL). The solution was concentrated to a small volume and then dissolved back up in tetrahydrofuran (1720 g). *H NMR (400 MHz/CDCl3) 5 7.79 (d, J= 3.02 Hz, 1H), 7.10 (d, J= 3.02 Hz, 1H), 5.81-5.70 30 (m, 1H), 5.20 (ddd, J= 1.78,3.02 10.43 Hz, 1H), 5.09 (ddd\ J= 1.9,3.2,171 Hz, 1H). 4 48 (t, /= 5.1 Hz, 1H), 4.00-3.95 (m, 2H), 3.43 (d, J= 5.1,2H), 3.41 (s, 6H). 26 WO 2006/019660 l,CI7US20O5/024447 Example 5E 2-(S)-Hydroxyamino-2-phenyl-ethanol A solution of (S)-phenylglycinol (15 g) and p-anisaldehyde (16.4g) in methyl ter/-butyl ether (150mL) was heated to reflux, with a Dean-Stark trap attached, for about 3 hours. 5 Tetrahydrofuran (60mL) was added and the mixture cooled to 0 °C. To this was added a solution of m-chloroperoxybenzoic acid (29.8 g) in methyl tert-butyl ether (80mL), maintaining the temperature below 5 °C. The mixture was stirred at 0 °C for about 3 hours. Then the reaction mixture was washed with 10% aqueous potassium carbonate (3 x 75mL). The resulting organic layer was concentrated to a smaller volume. To this was added a 10 solution of hydroxylamine hydrochloride (15.3 g) in methanol (19 mL) and water (27mL), and the reaction was stirred at room temperature for about 3 hours. Heptane (30mL) and water (30mL) were added. The layers were separated, and the aqueous layer was washed with methyl tert-butyl ether (3 x 30mL). The methanol was removed by vacuum distillation, and then methyl tert-butyl ether (75 ml) was added. After adjusting the pH to 7 with solid 15 potassium carbonate, sodium chloride was added and the layers separated. The aqueous layer was further extracted with methyl fert-butyl ether (2 x 75mL). The combined methyl tert-butyl ether extracts were filtered, concentrated to a small volume, and then heptane (70mL) was added. The resulting slurry was stirred at room temperature for about 1 hour and then cooled to 0 °C. After stirring for 1 hour, the mixture is filtered and the wetcake washed with 20 heptane (20mL). The wetcake was then dissolved in dichloromethane (lOOmL) for use in the next step.'H NMR (400 MHz, CDC13) 5 3.83-3.91 (2H, m), 4.12 (1H, dd, J= 6.9,4.8 Hz), 4.84 (3H, br s), 7.27-7.36 (5H, m). V3C NMR (100 MHz, CDC13) 8 63.8,67.7,127.5,127.9, 128.4,137.5. 25 Example 5F [Allyl-(5,6-dichloro-pvridin-3-yl)-amino]-acetaldehyde A solution of allyl-(5,6-6UcUoro-pyridm-3-vl)-(2,2-dimemoxy-emyl)-amine (57.2 g) in tetrahydrofuran (443 g) was cooled to 10 °C. A solution of concentrated hydrochloric acid (136 g) in water (114 g) was slowly added, maintaining the temperature below 20 °C. The 30 reaction was then stirred at 15 °C for about 4 hours. Then dichloromethane (570 g) and water (430 g) were added and the layers separated. The organic layer was washed with 5% aqueous 27 WO 2006/019660 PCT/US2005/024447 sodium bicarbonate (453 g), and then washed twice with water (430 g). The organic layer was concentrated and the residue dissolved in dichloromethane (580 g). Example 5G 5 (3S'.4S-2-[5-[5,6-Dichloro-pyridin-3-yl-hexahvdro-pyrrolo[3,4-c]isoxazol-l-yl]-2-(2’S- phenyl-ethanol (Compound 5G) 2-(S)-Hydroxyamino-2-phenyl-ethanol (13.8 g) was dissolved in dichloromethane (180 mL). To this was added magnesium bromide (15.9 g) and isopropyl alcohol (5.2 g). This mixture was stirred for 30 minutes, and then [allyl-(5,6-dichloro-pyridin-3-yl)-amino]- 10 acetaldehyde (18.4 g ) in dichloromethane (223 g) was added slowly. The reaction was stirred at 30 °C for about 5 hours. To the reaction was added 10% aqueous ammonium acetate (200mL). The layers were separated and then the organic layer was washed with water (200mL). The solution was concentrated to an oil, dissolved up in isopropyl alcohol (200mL) and concentrated to an oil. The resulting oil was dissolved in isopropyl alcohol 15 (l00mL) and heated to 80 °C to dissolve all the solids. The solution was cooled slowly to room temperature at which point heptane (l00mL) was added and the mixture heated to 60 °C. Upon cooling to room temperature, the mixture was filtered. After washing the wet cake with isopropyl alcohol, the product was dried in a vacuum oven. *H NMR (400 MHz/CDCl3) 8 7.51 (d, J= 2.7 Hz, 1H), 7.33 (m, 5H), 6.83 (d, J= 2.6 Hz, 20 1H), 4.11 (m, 1H), 3.80-3.91 (m, 3H), 3.74 (dd, J= 3.5,11.6 Hz, 1H), 3.32-3.40 (m, 3H), 3.12 (m, 2H). Example 5H (3S,4S)-5-(5,6-Dichloro-pyridin-3-yl)-hexahydro-pyrrolo[3.4-c]isoxazole (Compound 5HD 25 A solution of (35,4^2-[5-(5,6-dichloro-pyridin-3-yl)-hexahydro-pyrrolo[3,4- c]isoxazol-l-yl]-2-(2'S)-phenyl-ethanol (30 g) and triethylamine (11.2 g) in tetrahydrofuran (222 g) was cooled to 0 °C. Methanesulfonyl chloride (11.1 g) was slowly added and then the mixture was stirred at 5 °C for about 1 hour. A solution of sodium tert-butoxide (21.1 g) in tetrahydrofuran (133 g) was added and then the mixture stirred at room temperature for 30 about 2 hours. After adding water (44.5 g), the pH was adjusted to 7.9 with 3M aqueous hydrochloric acid (31 g). The solution was concentrated to about 90 mL, water (l00mL was added and then the pH was adjusted to 0.8 with 3M aqueous hydrochloric acid (28 g). The 28 WO 2006/01 0 PCT/US2005/024447 aqueous solution was washed with toluene/heptane (1:1; 2 x 150 ml). Isopropyl alcohol (150mL) was added and then the pH was adjusted to 4.4 with 10% aqueous potassium phosphate (55 g). The mixture was heated to 78 °C and then slowly cooled to 45 °C. Water (325 g) was slowly added and then the product was filtered. The wetcake was slurried in 5 isopropyl alcohol (75 mL) and water (68 mL), and then heated to 80 °C. The resulting solution was cooled slowly to 35 °C, at which point water (232mL) was slowly added. After stirring at room temperature for about 5 hours, the product was filtered, washed with isopropyl alcohol/.water (1:4; 30mL) and then dried in the vacuum oven. *H NMR (400 MHz/CDCl3) δ 7.68 (d, J= 2.9 Hz, 1H), 6.99 (d, J = 2.7 Hz, 1H), 4.32 (dt, J= 3.6,11.9 Hz, 10 1H), 3.99-3.83 (m, 2H), 3.61-3.52 (m, 2H). 3.39 (m, 1H), 3.34 (dd, J= 3.7,10.43 Hz, 1H), 3.29(dd,J=3.8,9.7Hz, 1H). Example 51 (3S,4S-[4-Amino-l-(5,6-dichloro-pyridin-3-yl)-pyrrolidin-3-yl]-methanol (Compound 5D 15 Raney Nickel (7.5 g) was charged to a Parr reactor. To this was added a solution of (35, 41S)-5-(5,6-dicUoro-pyridin-3-yl)-hexahydro-pyrrolo[3,4-c]isoxazole (50 g) in tetrahydrofuran (625 mL), ethanol (625 mL) and water (2mL). The mixture was hydrogenated at 40 psi and room temperature for about 3 hours. The reaction mixture was filtered through a bed of HyFlo and then concentrated to about l00mL. Isopropyl alcohol 20 (150mL) was added and this was concentrated to about l00mL. More isopropyl alcohol (l00mL) was added and then the mixture was heated to 80 °C. Heptane (250mL) was added, then the mixture was cooled to room temperature and filtered. After washing the wet cake with heptane, the product was dried in a vacuum oven-'H NMR (400 MHz/DMSO-d6) 5 7.61 (d, J= 2.8 Hz, 1H), 7.10 (d, J= 2.8 Hz, 1H), 3.63 (m, 2H), 3.50 (m, 1H), 3.43 (m, 1H), 3.30 25 (m, 2H), 3.13 (t, J = 9 Hz, 1H), 3.05 (dd, J= 3,10 Hz, 1H). Example 5J (1S, 5S)-3-(5,6-Dichloropyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane (Compound 5J) (3S,4S)-[4-Amino-1-(5,6-dichloro-pyridm-3-yl)-pyrrolidin-3-yl]-methanol (10 g) was 30 suspended in 1,2-drmethoxyetuane (100 mL) and N-methylpyyrolidinone'V1MEL). 1 he mixture was heated to 50 °C and then a solution of thionyl chloride (7.9 g) in 1,2-dimethoxyethane (35mL) was slowly added, while maintaining the temperature below 60 °C. 29 WO 2006/01 %60 PCT/US2005/024447 The reaction mixture was stirred at 50 °C for about 3 hours and then cooled to room temperature. After adding water (l00mL), the 1,1-dimethoxyethane was removed by distillation. Ethanol (l00mL) and water (l00mL) were added and the pH adjusted to 11-12 with 50% aqueous sodium hydroxide. The resulting mixture was heated at 60 °C for at least 5 12 hours and then cooled to room temperature. After filtering through a bed of Hy-Flo, the ethanol was removed by vacuum distillation. The pH was adjusted to >12 with 50% aqueous sodium hydroxide and then extracted with isopropyl acetate (2 x 80mL). The combined organic extracts were concentrated, and then suspended in isopropyl acetate (~50 mL). After heating to 80 °C, the solution was cooled to room temperature while stirring rapidly. The 10 suspension was cooled to 0 °C, filtered, washed with isopropyl acetate and dried in the vacuum oven. 1H NMR (MeOH-d4,, 300 MHz) δ 3.04 (dd, J=10.9,4.8 Hz, IH), 3.11 (dd, J=10.2,6.8 Hz, IH), 3.26 (dd, J=8.8,4.4 Hz, IH), 3.38 (m, IH), 3.73 (t, J=11.2 Hz, 2H), 3.84 (t, J=8.1 Hz, IH), 4.55 (dd, J=6.8, 4.8 Hz, IH), 7.37 (d, J=3.1 Hz, IH), 7.84 (d, J=2.7 Hz, IH); MS (DCI/NH3) m/z 244/246/248 (M+H)+. 15 Example 6 (1S,5S)-3-(5,6-Dichloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane acetate Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF 20 (anhydrous, 5 mL) was slowly added the solution of acetic acid (36 uL, 0.6 mmol) in THF (0.6 mL). The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (110 mg, yield, 72%). M.p. 160-164°C. Solubility: 13.4 mg/mL (water). 'H NMR (CD3QD, 300 MHZ) 5 1.91 (s, 3H), 3.08 (dd, J =10.5,6.4 Hz, IH), 3.13 (dd, J =12.2,4.8 Hz, IH), 3.43-3.52 (m, IH), 3.58 (dd, J =10.5,4.8 25 Hz, IH), 3.87 (d\ J =10.5 Hz, IH), 4.01 (d, J =11.8 Hz, IH), 4.14 (dd, J =10.5,8.5 Hz, IH), 4.91 (dd, J =7.1,4.7 Hz, IH), 7.49 (d, J =2.7 Hz, IH), 7.93 (d, J =2.7 Hz, IH) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+. Example 7 30 (IS, 5S-3-(5,6-Dicchloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]hectane hemicitrate Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of citric acid (115 mg, 0.6 mmol) in MeOH (0.6 mL). The 30 WO 2006/019660 l,CT/US2005/024447 mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (160 mg, yield, 94%). M.p. 165-172°C. Solubility: 15.7 mg/mL (water). *H NMR (CD3OD, 300 MHZ) 5 2.70 (d, J =15.2 Hz IH), 2.78 (d, J =15.2 Hz IH), 3.07 (dd, J =10.5, 6.5 Hz, IH), 3.16 (dd, J =12.2,4.7 Hz, IH), 3.44-3.54 (m, IH), 3.69 5 (dd, J =10.5,4.8 Hz, IH), 3.89 (d, J =10.5 Hz, IH), 4.11 (d, J =12.2 Hz, IH), 4.24 (dd, J =10.9, 8.5 Hz, IH), 5.03 (dd, J =7.2, 5.1 Hz, IH), 7.52 (d, J =3.0 Hz, IH), 7.95 (d, J =2.8 Hz, IH) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+. Example 8 10 (IS,5S)-3-(5>6-Dichloro-pvridin-3-yn-3,6-diaza-bicvclo[3.2.0]heptanemethanesulfonate Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of methylsulfonic acid (Aldrich, freshly prepared 1M in THF, 0.6 mL, 0.6 mmol). The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (110 mg, yield, 65%). M.p. 15 144-152°C. Solubility: >50 mg/ mL (water). lH NMR (CD30D, 300 MHZ) 8 2.69 (s, 3H)), 3.07 (dd, J =10.5, 6.5 Hz, IH), 3.18 (dd, J =12.2,4.7 Hz, IH), 3.44-3.52 (m, IH), 3.73 (dd, J =10.5,4.8 Hz, IH), 3.91 (d, J =10.5 Hz, IH), 4.11 (d, J =12.2 Hz, IH), 4.26 (dd, J =10.9,8.5 Hz, IH), 5.04 (dd, J =7.2, 5.1 Hz, IH), 7.54 (d, J =2.7 Hz, IH), 7.96 (d, J =3.0 Hz, IH) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+. 20 Example 9 (IS, 5S)-3-(5.6-Dichloro-pvridin-3-vl)-3.6-diaza-bicyclo[3.2.0]heptanemaleate Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of maleic acid (70 mg, 0.6 mmol) in MeOH (0.6 mL). 25 The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (140 mg, yield, 78%). M.p. 160-163°C. Solubility: 7.5 mg/mL (water). lH NMR (CD3OD, 300 MHZ) 5 3.07 (dd, J =10.5,6.5 Hz, IH), 3.18 (dd, J =12.2,4.7 Hz, IH), 3.44-3.56 (m, IH), 3.73 (dd, J =10.5,4.8 Hz, IH), 3.91 (d, J =10.5 Hz, IH), 4.11 (d, J =12.2 Hz, IH), 4.26 (dd, J =10.9,8.5 Hz, IH), 5.05 (dd, J =7.2 30 5.1 Hz, 1H), 6.27 (s, 2H), 7.53 (d, J =2.7 Hz, IH), 7.96 (d, J =2.9 Hz, IH) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+. 31 WO 2006/019660 PCT/US2005/024447 Example 10 (IS, 5SV3-(5t6-Dichloro-pvridin-3-vlV3.6-diaza-bicvclor3.2.01heptanenimarate Under N2, to a solution of the product of Example 5J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of fumaric acid (70 mg, 0.6 mmol) in MeOH (0.6 mL). 5 The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried (150 mg, yield, 84%). M.p. 198-202°C. Solubility: 2.9 mg/mL (water). lH NMR (CD30D, 300 MHZ) 5 3.07 (dd, J =10.5,6.5 Hz, IH), 3.17 (dd, J =12.2, 4.7 Hz, IH), 3.44-3.55 (m, IH), 3.71 (dd, J =10.5, 4.8 Hz, IH), 3.90 (d, J =10.5 Hz, IH), 4.11 (d, J =12.2 Hz, IH), 4.26 (dd, J =10.9, 8.5 Hz, IH), 5.04 (dd, J =7.2, 10 5.1 Hz, IH), 6.68 (s, 2H), 7.53 (d, J =3.1 Hz, IH), 7.96 (d, J =2.7 Hz, IH) ppm. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+. Example 11 (IS, 5SV3-(5,6-Dichloro-pyridin-3-ylV3,6-diaza-bicyclo|'3.2.0"|heptane hydrochloride 15 Under N2, to a solution of the product of Example 5 J (122 mg, 0.5 mmol) in THF (5 mL) was slowly added the solution of HCl (4M in dioxane, 0.15 mL, 0.6 mmol). The mixture was then stirred at ambient temperature for 6 h. White solid started to precipitate. The solid was then filtered and dried. MS (DCI/NH3) m/z 244 (M+H)+, 246 (M+H)+, 280 ( M+H+HCl), 282(M+H+HC1) 20 Example 12 (IS, 5S)-3-(5,6-Dichloro-pvridin-3-vlV3,6-diaza-bicvclof3.2.01heptane (L)tartrate To a solution of the product of Example 5 J (442 mg) in 5 J(442MG) methanol was slowly added a solution of L-tartaric acid (272 mg) in methanol (2 mL). During the addition, solids 25 started to crystallize. Upon completion of the addition, the slurry was stirred at room temperature for 10 minutes. The resulting mixture was then filtered and air-dried on the filter. lH NMR (D20,400 MHZ) δ 3.04 (dd, J = 10,6 Hz, IH), 3.21 (dd, J = 13,5 Hz, IH), 3.50-3.56 (m, 2H), 3.73 (m, IH) 3.83 (d, J = 11 Hz, IH), 4.07 (d, J = 13 Hz, IH) 4.29 (m, IH), 4.48 (s, 2H), 5.11 (m, IH), 7.49 (d, J = 3 Hz, IH), 7.85 (d, J = 3 Hz, 1H). 30 32 WO 2006/(11')66() l'd7US2005/024447 Example 13 (lS.5SV3-(5.6-Dichloro-pvridin-3-vlV3,6-diaza-bicvclo[3.2.01heplane(L)tartrale monohydrate A solution of the product of Example 12 (100 mg) in water (2 mL) was obtained by 5 sonicating for 30 seconds followed by heating to 70 °C. This solution was cooled to room temperature and then cooled in a methanol/dry-ice bath. After solids crystallized the slurry was stirred at 30 °C and then the mixture filtered to provide a white solid. Example 14 10 (lS,5S)-3-(5.6-Dichloro-pvridin-3-ylV3,6-diaza-bicvclo[3.2.0]heptane 4-methylbenzenesulfonate (Form ID The the product of Example 5J (500 mg) was dissolved in 1-propanol (10 mL). This solution was filtered through a 0.2-micron syringe filter. While this solution was stirred at room temperature, a solution of 4-methylbenzenesulfonic acid (324 mg) in 1-propanol (2 mL) 15 was added. After approximately 20 seconds, solids start to precipitate. The resulting slurry was stirred at room temperature for 1 hour, and then filtered. The wetcake was washed with 1-propanol (1 mL) and then dried overnight in a vacuum oven at 50 °C. The product was obtained as a white solid (614 mg). lH NMR (DMSO, 400 MHZ) d 2.27 (s, 3H), 2.96 (dd, J = 10,6 Hz, IH), 3.09 (dd, J = 12, 5 Hz, IH), 3.38 (m, IH), 3.56 (m, IH), 3.88 (d, J = 11 H 20 IH), 4.06-4.12 (m, 2H), 4.94 (m, IH), 7.08 (d, J = 8 Hz, 2H), 7.47 (d, J = 8 Hz, 2H), 7.51 (d, J = 3 Hz, IH), 7.94 (d, J = 3 Hz, IH). Example 15 (lS,5S)-3-(5.6-Dicchloro-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane 25 4-methyIbenzenesurfonate (Form II) A solution of the product of Example 3 A (441 mg) in 1-propanol (~7 mL) was treated with activated carbon (278 mg) and then filtered through a syringe filter. To this was added 4-methylbenzenesulfonic acid monohydrate (292 mg) and the resulting mixture heated to 70 °C. After stirring at 70 °C for 2.5 hours, more 4-methylbenzene sulfonic acid monohydrate 30 was added (75 mg). Alter 30 minutes more toluons sulfopic acid monohydrate was added (100 mg), and after 1 hour at 70 °C the reaction was complete. The resulting slurry was 33 WO2006/019660 PCT/US2005/024447 cooled to room temperature and filtered. The wetcake was washed with 1-propanol and air-dried to give a solid (440 mg). In Vitro Data 5 Determination of Binding Potency (lS,5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane was subjected to an vitro assay against the nicotinic acetylcholine receptor as described below. Binding of [3H]-cytisine ([3H]-CYT) to neuronal nicotinic acetylcholine receptors was accomplished using crude synaptic membrane preparations from whole rat brain (Pabreza et 10 al., Molecular Pharmacol., 1990, 39:9). Washed membranes were stored at -80 °C prior to use. Frozen aliquots were slowly thawed and resuspended in 20 volumes of buffer (containing: 120 mM NaCl, 5 mM KCL2 mM MgCl2,2 mM CaCl2 and 50 mM Tris-Cl, pH 7.4 @4 °C). After centrifuging at 20,000x g for 15 minutes, the pellets were resuspended in 30 volumes of buffer. 15 Each test compound was dissolved in water to make 10 mM stock solutions, diluted (1:100) with buffer (as above), and further taken through seven serial log dilutions to produce test solutions from 10'5 to 10"u M. Homogenate (containing 125-150 p.g protein) was added to triplicate tubes containing the range of concentrations of test compound described above and [3H]-CYT (1.25 nM) in a 20 final volume of 500 uL. Samples were incubated for 60 minutes at 4 °C, then rapidly filtered through Whatman GF7B filters presoaked in 0.5% polyethyleneimine using 3x4 mL of ice-cold buffer. The filters are counted in 4 mL of Ecolume® (ICN). Nonspecific binding was determined in the presence of 10 uM (-)-nicotine and values were expressed as a percentage of total binding. The IC50 value was determined with the RS-1 (BBN) nonlinear least squares 25 curve-fitting program and the IC50 value was converted to a Ki value using the Cheng and Prusoff correction (Kj=IC5o/(l+[ligand]/Kd of ligand). The Ki value for (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane was determined to be 0.10 nM. . In Vivo Data 30 Determination of Analgesic Effect Male Sprague Dawley rats (80-100 g) were purchased from Charles River (Portage, MT). Prior to surgery, animals were group-housed and maintained in a temperature regulated 34 WO 2006/019660 l,CT/US2005/024447 environment (lights on between 7:00 a.m. and 8:00 p.m.). Following nerve ligation surgery, animals were group housed. Rats had access to food and water ad libitum. The L5 and L6 spinal nerves of anesthesized rats were tightly ligated in the manner described previously by S.H. Kim and J.M. Chung, PAIN 50:355 (1992). Briefly, an incisio 5 was made on the dorsal portion of the hip and the muscle was blunt dissected to reveal the spinal processes. The L6 transverse process was removed, and the left L5 and L6 spinal nerves were tightly ligated with 5.0 braided silk suture. The wound was cleaned, the membrane sewn with 4.0 dissolvable Vicryl suture and the skin closed with wound clips. For the assessment of neuropathic pain, mechanical allodynia in the affected paw of 10 animals that had undergone spinal nerve ligation was evaluated using von Frey filaments. As described previously by S.R. Chaplan, F.W. Bach, J.W. Pogrel, J.M. Chung, and T.L. Yaksh, "Quantitative assessment of tactile allodynia in the rat paw" J. Neurosci. Meth., 53:55-63 (1994) two weeks following surgery, rats were acclimated to the testing box that was constructed of plexiglass with a wire mesh floor to allow access to the planter surface of the 15 hindpaws. Using the Dixons Up-Down method, a baseline level of allodynia was determined to have a withdrawal threshold of < 4 g of pressure. (lS,5S)-3-(5,6-Dichloro-3-pyridinyi)-3,6-diazabicyclo[3.2.0]heptane, administered intraperitoneally 15 minutes before testing, caused a dose-dependent increase in the withdrawal threshold up to a maximum effect of 15 g. The EC50 was determined to be 1 umol/kg. 20 Determination of Side Effect Liability Cells of the IMR-32 human neuroblastoma clonal line (ATCC, Rockville, MD) were maintained in a log phase of growth according to established procedures by R.J. Lukas, "Expression of ganglia-type nicotinic acetylcholine receptors and nicotinic ligand binding 25 sites by cells of IMR-32 human neuroblastoma clonal line" J. Pharmacol. Exp. Ther. 265:294-302 (1993). Cells were plated out at a density of lxlO6 cells per well on black-walled, clear-bottomed, 96-well plates (Costar, Cambridge, MA) and used approximately 72hours after plating. All plates were coated with polyethylenimine to aid in the adherence of the cells to the plate. 30 Changes in the intracellular Ca2* content of IMS. 32 cells were measured using the calcium chelating dye Fluo-4 (Molecular Probes, Eugene, OR) in conjunction with a Fluorescent Imaging Plate Reader (Molecular Devices, Sunnyvale, CA). The cell permeant 35 WO 2006/01«>660 PCT/US2005/024447 acetoxymethyl (AM) ester form of Fluo-3 was prepared to a concentration of I mM in anhydrous DMSO and 10% pluronic acid. The dye was then diluted to a final concentration of 4 mM in growth media and placed on the cells for I hour at 37 °C. Black-walled 96-well plates were utilized to reduce light scattering. The unincorporated dye was removed from the 5 cells by excessive washing with the assay buffer (HETES buffer, 20 mM Hepes, 120 mM NaCl, 5 mM KC1,1 AM MgCl2,5 mM glucose, 500 mM atropine, and 5 mM CaCl2). After addition of various concentrations of (lS5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane, the Ca2+ dynamics were observed in the Fluorescent Imaging Plate Reader (FLIPR) apparatus equipped with an Argon laser (wavelength, 480 nm), an 10 automated 96 channel pipettor and a CCD camera. The intensity of the fluorescence was captured by the CCD camera every second for the first minute following the agonist addition with additional readings every 5 seconds for a total time period of 5 minutes. These images were digitally transferred to an interfaced PC and change in fluorescence intensity processed for each well. The exposure setting of the camera was 0.4 sec with an f-stop setting of 2 15 microns. The percent maximal intensity relative to that induced by 100 p.M nicotine was plotted against the concentration of (lS5S)-3-(5,6-Dichloro-3-pyridinyl)-3,6- diazabicyclo[3.2.0]heptane and an EC50 value of 5.5 uM was calculated. Independent measurements of 100 μM nicotine (100%) and unloaded cells (0%) were performed on each plate of cells with an average range of 20,000 fluorescence units. (lS5S)-3-(5,6-Dichloro-3 20 pyridinyl)-3,6-diazabicyclo[3.2.0]heptane induced calcium efflux into IMR-32 cells with an EC50 of 5.5 μM, with a maximum efficacy 73% that of nicotine. The IMR-32 FLIPR assay, described herein, measures cation efflux that is mediated through the ganglionic-like nicotinic acetylcholine receptor (nAChR) subtype. Agents that facilitate cation efflux of the ganglionic nAChR subtype have been linked to side effect 25 liabilty such as cardiovascular pressor effects. For example, epibatidine, a known nAChRagent with cardiovascular pressor liability, was determined to have an EC50 of 24 nM and amaximal efficacy of 137% (compared to nicotine) in the IMR-32 FLIPR assay. Both the higher (less-potent) EC50 and the lower efficacy measured for (lS,5S)-3-(5,6-dichloro-3- pyridinyl)-3,6-dia2abicyclo[3.2.0]heptane demonstrate a reduced side effect liability for 30 (iyj5S)-3-(5,o-dicMoro-3-pyiiumyl)-3,6-diazabicycb[3.2.0]heptaneas compared to epibatidine. 36 WO 20(16/019660 PCT/US20O5/024447 The analgesic effect and the MR-32 activity of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]hcptane was compared to related analogs as illustrated in Table 1. 37 Table 1 W<)20CT/tJS2005/024447 pyridinyl)-3,6-diazabicyclo[3.2.0]hcptane or a pharmaceutically acceptable salt or prodrug thereof, in combination with a tricyclic antidepressant. 15. A pharmaceutical composition for treating pain in a mammal comprising administering to a mammal a therapeutically effective amount of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane or a pharmaceutically acceptable salt or prodrug thereof, in combination with an anticonvulsant. 16. A salt of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, or a prodrug thereof, selected from the group consisting of acetate, citrate, fumarate, hemicitrate, hydrochloride, maleate, methanesulfonate, 4-methylbenzenesulfonate, sulfate, L-tartrate, and trifluoroacetate. 17. A substantially pure salt of (lS,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane, or a prodrug thereof, selected from the group consisting of acetate, citrate, fumarate, hemicitrate, hydrochloride, maleate, methanesulfonate, 4-methylbenzenesulfonate, sulfate, L-tartrate, and trifluoroacetate. 18. A process for preparing compound. (5 J), comprising the steps of: 53 a) treating compound (5D), WO 2006/019660 PCT/US2005/02-M47 with an aqueous acid;. b) treating the mixture from step (a) with a compound of formula (A), wherein Rz is phenyl optionally substituted with alkyl, alkoxy or halo in the presence of magnesium bromide in a mixture of isopropyl alcohol and dichloromethane to provide a compound of formula (B), c) using the compound of formula (B) to preparing the compound (5 J). 19. The process of claim 18, wherein compound (5J) is prepared from the compound of formula (B) by a process comprising the steps of: a) treating the compound of formula (B) with a reagent that will convert the hydroxyl group into a leaving group; b) treating the compound from step (a) with potassium tert7butoxide under heated conditions; 54 WO 2006/019660 PCT/US2005/024447 c) treating the compound from step (b) with an aqueous acid to obtain a pH < 1 followed by adjusting the pH to 4-5 to provide compound (5H), d) using compound (5H) to prepare compound (5J). 20. A process for preparing a compound (5J) comprising the steps of: a) treating compound (5H) with Raney Nickel under a 4C PSI atmosphere of hydrogen in a solvent to obtain compound (5D, 55 WO 2006/019660 PCT/US2005/024447 treating compound (51) with N-methylpyrrolidinone in 1,2-dimethoxyethane at 50 °C with SOCl2 for 3 hours; and c) treating the mixture from step (b) with NaOH to obtain compound (5 J). 56