6-BroMo-1-Methyl-1H-pyrazolo[4,3-b]pyridine

To a solution of 6-bromo-1H-pyrazolo[4, 3-b]pyridine (400 mg, 2.02 mmol) in DMF (10 mL) at 0 oC was added 60percent NaH in mineral oil (80.8 mg, 2.02 mmol) and the mixture was stirred at rt for 30 mm. A solution of Mel (287 mg, 2.02 mmol) in DMF (5 mL) was added and the mixture was stirred at rt for 30 mm. Then the mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2504, filtered and concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC to give 6-bromo-1-methyl-1H-pyrazolo[4, 3-b]pyridine as a white solid (150 mg, 35percent). 1HNMR (300 MHz, DMSO-d6) 8.58-8.60 (m, 2H), 8.30-8.3 1 (m, 1H), 4.06 (s, 3H).To a solution of 6-bromo-2H-pyrazolo[4, 3-b]pyridine (1.5g, 7.57 mmol) in DMF (30 mL) was added sodium hydride (60%, 0.364 g, 9.09 mmol) at 0 C. The reaction mixture was stirred for 30 min before iodomethane (3.23 g, 22.72 mmol) was added the reaction mixture was stirred at 0 C for 4 h. The reaction was diluted with aqueous NH4Cl (saturated, 50 mL) and extracted with EtOAc (50 mL x 4). The combined organic fractions were washed with water (100 mL x 3), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-40% THF/petroleum ether) to give the title compound as the lower eluting product (Rf = 0.60, 1:1 EtOAc:petroleum ether).1H NMR (400 MHz, methanol-d4): delta 8.57 (1 H, d, J = 1.6, Hz), 8.19 (1 H, d, J = 9.9 Hz), 4.26 (3 H, s), as well as the regioisomeric product, 6-bromo-1-methyl-1H-pyrazolo[4, 3-b]pyridine as the higher eluting product (Rf = 0.30, 1:1 EtOAc:petroleum ether).1H NMR (400 MHz, methanol-d4): delta 8.41 (1 H, d, J = 1.6, Hz), 8.20 (1 H, s), 7.95 (1 H, s), 4.08 (3 H, s).A solution of 6-bromo-lH-pyrazolo[4, 3-]pyridine (500 mg, 2.52 mmol) and cesium carbonate (1234.04 mg, 3.79 mmol) in DMF (7.5 mL) was stirred at r.t. lodomethane (189 mu, 3.03 mmol) was added and the reaction mixture was stirred for 1.5 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between water (25 mL) and EtOAc (25 mL). The aqueous phase was further extracted with EtOAc (25 mL). The combined organic phase was washed with brine (25 mL), then dried over MgS04 and filtered. The solvent was removed in vacuo to give the title compounds (584.8 mg) as a 7:3 mixture of regioisomers, which was used in the next step without further separation. Method B HPLC-MS: MH+ mlz 212/214, RT 1.47 minutes (26%) and 1.56 minutes (72%)To a solution of

Molecular Weight:212.05
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Exact Mass:210.97451
Monoisotopic Mass:210.97451
Topological Polar Surface Area:30.7
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes