Tert-butyl 5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylpyridin-2-ylcarbamate → N-(7-(6-amino-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

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Reaction Steps

A solution of the crude tert-butyl 5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylpyridin-2-ylcarbamate in dichloromethane (4 mL) and trifluoroacetic acid (4 mL) was stirred for 60 mins at ambient temperature and concentrated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate and brine and extracted twice with dichloromethane, and the combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, ISCO, 0.5-20% methanol in dichloromethane) and subsequently repurified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid) to afford the title compound as a white amorphous solid (7.0 mg, 12% over 2 steps). 1H NMR (400 MHz, DMSO) δ 10.86 (s, 1H), 9.14 (s, 1H), 8.46 (s, 1H), 7.94 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.84, (s, 1H), 7.66 (dd, J=8.8, 1.4 Hz, 1H), 6.40 (s, 1H), 5.91 (s, 2H), 2.17 (s, 3H), 2.12-2.03 (m, 1H), 0.90-0.79 (m, 4H). LCMS (Method E): RT=3.241 min, M+H+=319.1.

Provenance & Evidence