1H-Imidazole, 4-(chloromethyl)-1-methyl-, hydrochloride (1:1)

To a solution of intermediate 1 (5g, 44.64 [MMOL)] in CH2CI2 [(10 MI)] at [0°C] was added dropwise thionyl chloride (50 [ML)] and then the mixture was stirred at room temperature overnight and then under reflux for 3 hours and then concentrated under reduced pressure. The residue was treated with diethyl oxide and the resulting precipitate was filtered and dried. The title compound was obtained as a brown solid [(4G, ] 53. 80percent); 1HNMR (300 MHz, [DS-DMSO, PPM). S] : 9.25 (s , 1H), 7.8 (s, 1H), 4.95 (s, 2H), 3.9 (s, 3H).To a solution of intermediate 22 (5g, 44.64 [MMOL)] in [CH2CI2] (10 ml) at [0°C] was added dropwise thionyl chloride (50 mi) and then the mixture was stirred at room temperature overnight and then at reflux for 3 hours. The mixture was concentrated under reduced pressure, and diethyl ether added. The resulting precipitate was filtered and dried to give the title product as a brown solid (4g, 53. [81percent) ;APOS;H] NMR (300 MHz, [D6-DMSO)] [] ppm: 9.25 (s, [1 H), ] 7.8 (s, 1H), 4. 95 (s, 2H), 3.9 (s, 3H).To a solution of intermediate 6 (5g, 44.64 [MMOL)] in CH2CI2 (10 ml) at [0°C] was added dropwise thionyl chloride (50 mi) and the mixture was stirred at room temperature overnight and then at reflux for 3 hours. The mixture was concentrated under reduced pressure and the residue taken up in diethyl ether to give a precipitate. The precipitate was filtered and dried to give the title compound [(4G, ] 53. [81 percent) ;APOS;H] NMR (300 MHz, [DMSO-D6)] [6] ppm : 9.25 (s, [1 H), ] 7.8 (s, [1 H), ] 4.95 (s, 2H), 3.9 (s, [3H).]General procedure: To a solution of 4-chloro-lH-pyrrolo-[3, 2-c]-pyridine [60290-21-3] (2.0 g, 13.1 mmol) dissolved in DMF (30.5 mL, 0.944 g/mL, 393.2 mmol) at 0C was added portionwise sodium hydride (1.1 g, 28.8 mmol). The reaction mixture was allowed to reach rt and stirred 45 min, after which it was re-cooled to 0C and l-bromobutane (2.1 mL, 1.27 g/mL, 19.7 mmol) was added dropwise. The mixture was then allowed to reach rt and stirred overnight. NaHC03 sat solution was added and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with water and brine, then dried over MgS04 and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel; gradient Heptane/EtOAc from 100/0 to 50 /50) to yield 1-1 (2.7 g, 98.7%) as a yellow liquidA mixture of 4-(6-fluoropyridin-3-yl)-6-hydroxypyrazolo[l, 5-a]pyridine-3- carbonitrile (Intermediate P66, 103.6 mg, 0.4075 mmol), 4-(chloromethyl)-l-methyl-lH- imidazole hydrochloride (199.7 mg, 1.196 mmol) and Cs2CCb(s) (1.328 g, 4.075 mmol) in DMA (2.0 mL) was stirred for 1 d at 60 C, then for an additional 1 d at 110 C. After cooling to ambient temperature, the reaction mixture was acidified with 2 M HCl(aq), and purified directly by C18 reverse phase chromatography (using 0-70% water/ ACN with 0.1% TFA as the gradient eluent). Fractions containing the desired product were combined, partially concentrated in vacuo to remove the ACN, then partitioned between saturated NaHC03(aq) and 4: 1 DCM:iPrOH. The biphasic mixture was extracted with additional 4: 1 DCM:iPrOH (3x). The combined organic extracts were dried over anhydrous Na2S04(S), filtered and concentrated in vacuo to afford the title compound (26.0 mg, 18% yield). MS (apci) m/z = 349.10 (M+H).To a solution of intermediate 42 (0.4g, 1. 02mmot) in DMF (20ml) was added portionwise sodium hydride (60% in mineral oil, 101mg, 2. [55MMOL)] and the mixture was stirred at room temperature for 20 minutes. Intermediate 7 (173mg, 1. [32MMOL)] was then added and the mixture was heated at [60C] for 3 days. The reaction mixture was poured into water and extracted with [CH2CI2. THE] combined organic extracts were separated, dried over [NA2SO4, ] filtered and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with CH2CI2/MeOH (90: 10), to give (after trituration with diisopropyl ether), the title compound as a yellow solid (130mg, 26%); m. p. [217C] ; TOF MS ES exact mass calculated for [CSOHZENEO] [: 487.] 2246 (MH+). Found: 487.2247 (MH+).EXAMPLE 4 4-(3-Chloro-2-pyridinylthiomethyl)-1-methyl-1H-imidazole dihydrochloride To a solution of sodium (90.6 mg, 3.94 mmol) in 10 ml of ethanol was added 3-chloro-2-thiopyridine (286 mg, 1.97 mmol) and the reaction was stirred ten minutes. A solution of To a solution of intermediate 1 (5g, 44.64 [MMOL)] in CH2CI2 [(10 MI)] at [0°C] was added dropwise thionyl chloride (50 [ML)] and then the mixture was stirred at room temperature overnight and then under reflux for 3 hours and then concentrated under reduced pressure. The residue was treated with diethyl oxide and the resulting precipitate was filtered and dried. The title compound was obtained as a brown solid [(4G, ] 53. 80percent); 1HNMR (300 MHz, [DS-DMSO, PPM). S] : 9.25 (s , 1H), 7.8 (s, 1H), 4.95 (s, 2H), 3.9 (s, 3H).To a solution of intermediate 22 (5g, 44.64 [MMOL)] in [CH2CI2] (10 ml) at [0°C] was added dropwise thionyl chloride (50 mi) and then the mixture was stirred at room temperature overnight and then at reflux for 3 hours. The mixture was concentrated under reduced pressure, and diethyl ether added. The resulting precipitate was filtered and dried to give the title product as a brown solid (4g, 53. [81percent) ;APOS;H] NMR (300 MHz, [D6-DMSO)] [] ppm: 9.25 (s, [1 H), ] 7.8 (s, 1H), 4. 95 (s, 2H), 3.9 (s, 3H).To a solution of intermediate 6 (5g, 44.64 [MMOL)] in CH2CI2 (10 ml) at [0°C] was added dropwise thionyl chloride (50 mi) and the mixture was stirred at room temperature overnight and then at reflux for 3 hours. The mixture was concentrated under reduced pressure and the residue taken up in diethyl ether to give a precipitate. The precipitate was filtered and dried to give the title compound [(4G, ] 53. [81 percent) ;APOS;H] NMR (300 MHz, [DMSO-D6)] [6] ppm : 9.25 (s, [1 H), ] 7.8 (s, [1 H), ] 4.95 (s, 2H), 3.9 (s, [3H).]

Molecular Weight:167.03
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:166.0064537
Monoisotopic Mass:166.0064537
Topological Polar Surface Area:17.8
Heavy Atom Count:9
Complexity:76.8
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes