Methylamine → 5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-N,4-dimethylpicolinamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(7-(6-chloro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (50 mg, 0.1 mmol), palladium acetate (2 mg, 0.007 mmol), 1,3-bis(dicyclohexylphosphino)propane bis(tetrafluoroborate) (9 mg, 0.014 mmol), potassium carbonate (29 mg, 0.21 mmol), methylamine (2.0M solution in tetrahydrofuran, 0.74 mL), and N,N-dimethylformamide (1 mL) was purged with nitrogen and evacuated (3×), flushed with carbon monoxide and evacuated (2×), and then left under a carbon monoxide balloon and heated at 100° C. for 2 hours. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (25 mg, 50%). 1H NMR (400 MHz, DMSO) δ 10.94 (s, 1H), 9.21 (s, 1H), 8.79 (m, 1H), 8.54 (s, 1H), 8.52 (s, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.98 (d, J=8.6 Hz, 1H), 7.78 (d, J=8.7 Hz, 1H), 2.85 (d, J=4.8 Hz, 3H), 2.41 (s, 3H), 2.14-2.03 (m, 1H), 0.92-0.78 (m, 4H). LCMS (Method E): RT=4.054 min, M+H+=361.1.

Provenance & Evidence