反应详情

温度

25 °C

A 2M solution of methylamine in methanol (0.535 ml) was added to a mixture of 2-[2-amino-5-[1-(1-tert-butoxycarbonyl-4-piperidyl)pyrazol-4-yl]-3-pyridyl]-1,3-benzoxazole-7-carboxylic acid (270 mg) and bis(dimethylamino)methylene-(triazolo[5,4-b]pyridin-3-yl)oxonium hexafluorophosphate (285 mg) dissolved in DMF (1 ml). The resulting solution was heated at 25° C. for 1 day. A 2N solution of methylamine (0.535 ml) in methanol was added and the mixture was stirred at 25° C. in a sealed tube for 3 days. The mixture was evaporated to dryness and adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 20 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-[7-(methylcarbamoyl)-1,3-benzoxazol-2-yl]-3-pyridyl]pyrazol-1-yl]piperidine-1-carboxylate (210 mg) as a pale yellow solid. NMR Spectrum: (DMSOd6) 1.43 (s, 9H), 1.80 (dd, 1H), 1.85 (dd, 1H), 2.01-2.11 (m, 2H), 2.94 (bs, 2H), 2.96 (d, 3H), 4.00-4.13 (m, 2H), 4.36-4.46 (m, 1H), 7.51 (dd, 1H), 7.65 (bs, 2H), 7.82 (dd, 1H), 7.93 (s, 1H), 7.98 (dd, 1H), 8.30 (s, 1H), 8.43 (q, 1H), 8.54 (d, 1H), 8.57 (d, 1H); Mass spectrum: M+H+ 518.

1. customThe mixture was evaporated to dryness
2. customThe crude product was purified by flash chromatography on silica gel eluting with 20 to 50% ethyl acetate in petroleum ether
3. customThe solvent was evaporated to dryness