1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Steps

A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 1-methylcyclopropanamine (0.04 g, 0.56 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature for 5 hours, and then HATU (0.114 g, 0.3 mmol) was added. The final reaction mixture was stirred for another 15 hours. The solvent was removed under reduced pressure at 70° C. The residue was triturated with water and then 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: 50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 80% acetonitrile/20% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.035 g, 43%) as a white solid. MS: (M+H)+=381; 1H NMR (300 MHz, DMSO): δ 12.87 (s, 1H), 9.11 (s, 1H), 8.55 (s, 1H), 8.46-8.44 (m, 2H), 8.04 (s, 1H), 7.38 (d, 1H, J=8.7 Hz), 4.20 (s, 3H), 1.50 (s, 3H), 0.90-0.82 (m, 4H).

Provenance & Evidence