反应详情

tert-Butyl [1-(6-chloropyridin-2-yl)piperidin-4-yl]carbamate (Intermediate 66) (300 mg, 0.99 mmol) was dissolved in 0.5 M solution of sodium methoxide in MeOH (9 ml, 4.45 mmol) at room temperature and the mixture was refluxed for 72 h. The solvent was removed in vacuo, extracted with EtOAc then washed with water. The organic phase was concentrated in vacuo and treated with 4 N hydrochloric acid in dioxane (10 ml) for 2 h. The solvent was removed in vacuo and dried to remove excess hydrochloric acid. The solid was dissolved in NMP (3 ml) and pentafluorophenyl 4-bromo-5-methyl-1H-pyrrole-2-carboxylate (Intermediate 17) (80 mg, 0.216 mmol) and TEA (137 μl, 0.9 mmol) were added. The mixture was stirred at room temperature for 2 h and the mixture was purified by semi-preparative HPLC using a gradient of 15-95% CH3CN/H2O (0.1% TFA) to give the title compound (23 mg).

1. temperaturethe mixture was refluxed for 72 h
2. customThe solvent was removed in vacuo
3. extractionextracted with EtOAc
4. washthen washed with water
5. concentrationThe organic phase was concentrated in vacuo
6. additiontreated with 4 N hydrochloric acid in dioxane (10 ml) for 2 h
7. customThe solvent was removed in vacuo
8. customdried
9. customto remove excess hydrochloric acid
10. dissolutionThe solid was dissolved in NMP (3 ml)
11. customthe mixture was purified by semi-preparative HPLC