反应详情

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), 2-cyclopropylpropan-2-amine hydrochloride (0.05 g, 0.37 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. Then HATU (0.114 g, 0.3 mmol) was added, the final reaction mixture was stirred for additional 15 hour. The mixture was poured into 30 mL of water with stirring. After 30 minutes, the mixture was 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 65% acetonitrile/35% 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-(2-cyclopropylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=409; 1H NMR (300 MHz, DMSO): δ 12.81 (s, 1H), 9.04 (s, 1H), 8.41-8.38 (m, 2H), 7.95-7.87 (m, 2H), 7.21 (d, 1H, J=7.2 Hz), 4.15 (s, 3H), 1.53-1.20 (m, 7H), 0.42 (brs, 4H).

1. customthe final reaction mixture
2. stirringwas stirred for additional 15 hour
3. stirringwith stirring
4. waitAfter 30 minutes
5. filtrationthe mixture was filtered
6. customthe filter cake was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
7. wait35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 65% acetonitrile/35% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.