Trifluoroacetic acid → HCID 71115154, compound

Participants

Reaction Steps

To a solution of (1S,2S)-N-(7-(5-amino-4-methylpyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide (46.2 mg; 0.137 mmol) in trifluoroacetic acid (1.0 mL; 13 mmol) at 0° C. was added N-amyl nitrite (29 μL; 0.21 mmol). The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated, and then partitioned between dichloromethane and 2 M aqueous sodium carbonate. The aqueous layer was neutralized to pH 7 with citric acid, and then extracted twice more with dichloromethane. The combined dichloromethane layers were dried over magnesium sulfate and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane) followed by preparatory reverse-phase HPLC to yield 8.4 mg (18%) of the title compound. LCMS (ESI): RT (min)=3.583, M+H=338.1, method=E; 1H NMR (400 MHz, DMSO) δ 10.96 (s, 1H), 9.94 (broad s, 1H), 9.19 (s, 1H), 8.52 (s, 1H), 8.15 (s, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.96 (d, J=8.6 Hz, 1H), 7.71 (d, J=8.5 Hz, 1H), 4.95 m, 1H), 2.27 (m, 1H), 2.12 (s, 3H), 1.70 (m, 1H), 1.20 (m, 1H).

Provenance & Evidence