反应详情

温度

0 °C

Over a period of 5 minutes, a solution of 1-(1-acetylpiperidin-4-yl)-4-(6-amino-5-(1,3-benzoxazol-2-yl)pyridin-3-yl)-1H-pyrazole-3-carbaldehyde (132 mg) in MeOH/dichloromethane (1:1) that had been cooled to 0° C., was added to a stirred solution of methylamine (0.153 ml, 0.31 mmol) dissolved in dichloromethane (6 ml) and methanol (6 ml). The resulting solution was stirred at 0° C. for 20 minutes. Sodium triacetoxyhydroborate (78 mg) was added at 0° C. to the mixture and stirred at 0° C. for 5 hours. The mixture was evaporated. A saturated solution of sodium bicarbonate was added and the mixture was extracted with methylene chloride, dried over magnesium sulphate, filtered and evaporated under reduced pression. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 micron silica, 19 mm diameter, 100 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness, tritured with hot acetonitrile, filtered and dried under reduce pressure to afford 1-[4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(methylaminomethyl)pyrazol-1-yl]-1-piperidyl]ethanone (23 mg) as a solid. NMR Spectrum: (CDCl3) 1.86-2.11 (m, 2H), 2.15 (s, 3H), 2.13-2.24 (m, 1H), 2.24-2.33 (m, 1H), 2.60 (s, 3H), 2.73-2.84 (m, 1H), 3.21-3.32 (m, 1H), 3.96 (s, 2H), 3.97-4.06 (m, 1H), 4.31-4.42 (m, 1H), 4.70-4.85 (m, 1H), 6.97 (bs, 2H), 7.32-7.41 (m, 2H), 7.54 (s, 1H), 7.57 (dd, 1H), 7.73 (dd, 1H), 8.32 (s, 1H), 8.42 (s, 1H); Mass spectrum: M+H+ 446;

1. stirringstirred at 0° C. for 5 hours
2. customThe mixture was evaporated
3. additionA saturated solution of sodium bicarbonate was added
4. extractionthe mixture was extracted with methylene chloride
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. customevaporated under reduced pression
8. customThe reaction mixture was purified by preparative HPLC
9. customThe fractions were evaporated to dryness, tritured with hot acetonitrile
10. filtrationfiltered
11. customdried