Formamide → 1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]phenyl}phenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide

Participants

Reaction Steps

A solution of 1-(4-methoxy-phenyl)-6-(2′-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (57, 13.5 g, 26.4 mmol) in DMF (50 mL) was treated with formamide (8.32 g, 6.2 mL, 184.8 mmol, 7.0 equiv) at room temperature, and the resulting reaction mixture was cooled down to 0–5° C. before being treated dropwise with a solution of MeONa (8.6 g, 9.05 mL, 39.6 mmol, 1.5 equiv) in methanol at 0–5° C. The resulting reaction mixture was stirred at 0–5° C. for 30 min before being gradually warmed up to room temperature for an additional 3 h. When HPLC and TLC showed the reaction was complete, the reaction mixture was slowly poured into water (600 mL). The resulting mixture was then stirred at room temperature for 1 h to precipitate the desired product. The solids were collected by filtration, washed with water (2×100 mL) and methyl tert-butyl ether (2×100 mL), dried in vacuo at 40–45° C. for 12 h to afford crude desired 1-(4-methoxy-phenyl)-6-(2′-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid amide (58, 10.55 g, 12.71 g theoretical, 83%). This crude solids were subsequently recrystallized in a mixture of ethanol and methanol to afford the pure product. For 58, CIMS m/z 482 (M++H, C28H27N5O3).

Provenance & Evidence