Water → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclohexyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Steps

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (70 mg, 0.22 mmol) in 6 mL of DMF were added EDCI (64 mg, 0.33 mmol) and DMAP (42 mg, 0.34 mmol), followed by the addition of 1-methylcyclohexanamine hydrochloride (50 mg, 0.33 mmol) in one portion at room temperature and stirred for 16 hours. The reaction mixture was poured into 35 mL of water, and filtered to give a crude product, which was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 55% acetonitrile/45% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 88% acetonitrile/12% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclohexyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (26 mg, 28.4%) as a pale yellow solid. MS: (M+H)+=407; 1H NMR (300 MHz, DMSO): δ 12.68 (s, 1H), 9.10 (s, 1H), 8.45-8.40 (m, 2H), 7.85 (s, 1H), 7.71 (d, 1H, J=9.9 Hz), 7.20-7.14 (m, 1H), 4.17 (s, 3H), 2.33-2.29 (m, 2H), 2.03-2.00 (m, 1H), 1.53-1.46 (m, 10H).

Provenance & Evidence