Sodium hydride → 3-Amino-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

Participants

Reaction Steps

To a stirred solution of 4-cyclopropylamino-nicotinonitrile (2.15 g, 13.51 mmol) and methyl bromoacetate (1.53 mL, 16.21 mmol, 1.2 eq) at 0° C. was added sodium hydride (60% in mineral oil: 1.35 g, 33.78 mmol, 2.5 eq) portion wise over 15 min. After the evolution of hydrogen gas had subsided, the reaction mixture was warmed to ambient temperature and stirred under N2 for 16 h. The reaction mixture was quenched with saturated NH4Cl solution (10 mL) and poured into EtOAc. The biphasic layers were separated, and the organic layer was washed with 50% aq. brine, sat. NaHCO3 solution, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was absorbed onto silica and purified by flash column chromatography (silica, ISCO, 45 mL/min, 0 to 25% MeOH in EtOAc) to give the desired product as an orange solid (1.57 g, 50.3%). 1H-NMR (500 MHz, DMSO-d6) δ ppm 9.01 (d, J=1.0 Hz, 1H), 8.24 (t, J=5.1 Hz, 1H), 7.29 (dd, J=6.0 Hz, J=1.0 Hz, 1H), 6.34-6.09 (br s, 2H), 3.85 (s, 3H), 3.35 (m, 1H), 1.14-1.03 (m, 2H), 0.80-0.70 (m, 2H); LC-MS (method D): [M+H]+=232.0, RT=1.31 min.

Provenance & Evidence