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

関与物質

反応手順

To a stirred solution of 2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.34 mmol), DIEA (200 mg, 1.55 mmol), EDCI (123 mg, 0.64 mmol) and DMAP (110 mg, 0.90 mmol) in 6 mL of DMF was added 1-aminocyclopropanecarbonitrile hydrochloride (100 mg, 0.84 mmol) in one portion at room temperature, then the mixture was stirred for 16 hours. The reaction mixture was poured into 40 mL of water, filtered and the filter cake 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: 35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give N-(1-cyanocyclopropyl)-2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (5 mg, 4.1%) as a yellow solid. MS: (M+H)+=358; 1H NMR (300 MHz, DMSO): δ 13.40 (s, 1H), 13.00 (s, 1H), 9.19 (s, 1H), 8.98 (s, 1H), 8.56 (d, 1H, J=3.0 Hz), 8.38 (d, 1H, J=8.1 Hz), 7.46 (s, 1H), 7.21 (d, 1H, J=8.4 Hz), 2.53 (s, 3H), 1.78-1.74 (m, 2H), 1.48-1.44 (m, 2H).

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