4-Chloro-1-methyl-1H-imidazo[4,5-c]pyridine

To a solution of 4chloro.3H—imidazo[45--cipyridine (100 rng, 0.65 mmol) in DMF (3 mL) was added NaH (78 mg, I .9SmmoI, 6() wtpercent in oil)at 0°C under N2. The mixture was stirredat 0°C tbr 40 minutes. Mel (277 mg, 1 .95 mmol) was added at 0°C. And the mixture was stirred for another 2 hours at RT. The mixture was quenched with saturated NH4CI aqueous solution, extracted with EtOAc (20 mL x3). The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by PrepHPLC to give thetitle compound 58 (40.3 mg) as yellow oil, compound 59 (41.0 mg) as yellow oil. LRMS mlz M+H) 168.2, 170.2 found, 168, 0, 170.2 required.To a solution of 4-chloro-3i7-imidazo[4, 5-c]pyridine (1 g, 6.51 mmol, CAS 81053- 66-9) in DMSO/THF (2.5 mL/25 mL) was added NaHMDS (9.76 mL, 9.76 mmol) at 20 C under N2. The reaction mixture was stirred at 20 C for 1 h. Then, to the reaction mixture was added Mel (1.21 mL, 19.5 mmol) at 20 C. The reaction mixture was then stirred at 20 C for 11 h. The reaction mixture was filtered and the filtrate was concentrated to give a residue. The residue was purified by prep-HPLC (NH3 H20) to give 4-chloro-l -methyl- H- imidazo[4, 5-c]pyridine (Intermediate DG) (257.2 mg, 24% yield) as a white solid, LCMS (ESI+) m/z: 167.8 (M+H)+; 1HNMR (400MHz, DMSO-i) d 8.16-8.14 (m, 1H), 7.92 (s, 1H), 7.27-7.25 (m, 1H), 3.71 (s, 3H), and 4-chloro-3-methyl-3if-imidazo[4, 5-c]pyridine (Intermediate DH) (201.8 mg, 19% yield) as a white solid, LC-MS (ESI+) m/z: 167.8 (M+H)+, 1HNMR (400MHz, DMSO-i) d 8.34-8.13 (m, 1H), 7.98 (m, 1H), 7.79-7.54 (m, 1H), 7.29 (m, 1H), 4.34-4.09 (m, 3H).To a solution of 4chloro.3H-imidazo[45--cipyridine (100 rng, 0.65 mmol) in DMF (3 mL) was added NaH (78 mg, I .9SmmoI, 6() wt% in oil)at 0C under N2. The mixture was stirredat 0C tbr 40 minutes. Mel (277 mg, 1 .95 mmol) was added at 0C. And the mixture was stirred for another 2 hours at RT. The mixture was quenched with saturated NH4CI aqueous solution, extracted with EtOAc (20 mL x3). The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by PrepHPLC to give thetitle compound 58 (40.3 mg) as yellow oil, compound 59 (41.0 mg) as yellow oil. LRMS mlz M+H) 168.2, 170.2 found, 168, 0, 170.2 required.A mixture of compound 59 (the product form step 1) (300 mg, 1.80 mmol) and NH4OAc (3, 20 g) in acetic acid (4 mL) was stirred at 120C for 16 hours, After cooling to RI?, the mixture was adjusted to p1-l=- 7 with saturated Nal-IC )3 aqueous solution and extracted with EtOAc (2OmL x 3), DCM (20 mL x 3), DCM: i-Propanoi = 4:1 (30 mL x 3), respectively. The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound (500 mg) as yellow solid. LRMS m/z (M+H) 150.1 found, 150.1 required.

Molecular Weight:167.59
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Exact Mass:167.0250249
Monoisotopic Mass:167.0250249
Topological Polar Surface Area:30.7
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes