反应详情

温度

75 °C

Sodium hydrogen carbonate (28.6 mg) was added to a solution of (2S)-1-(1,3-benzoxazol-2-y1)-N2-[(3S)-pyrrolidin-3-yl]-2-piperidinecarboxamide (104.9 mg) [see Example 4] and 2-bromopyridine (52.7 mg) in acetonitrile (5 ml). The reaction mixture was heated to 75° C. for 48 hours, after which time additional sodium hydrogen carbonate (28.6 mg) was added and the mixture was heated under reflux for a further 24 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water, the organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 93:7:1, by volume, dichloromethane:methanol: 0.88 aqueous ammonia solution, and was then further purified by a second column eluting with 95:5, by volume, ethyl acetate:diethylamine to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-1-(2-pyridinyl)pyrrolidin-3-yl]-2-piperidinecarboxamide (11 mg) as a brown oil.

1. temperaturethe mixture was heated
2. temperatureunder reflux for a further 24 hours
3. customThe solvent was removed under reduced pressure
4. customthe residue was partitioned between ethyl acetate and water
5. customthe organic layer was separated
6. dry with materialdried over magnesium sulphate
7. customthe solvent removed under reduced pressure
8. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 93:7:1, by volume, dichloromethane
9. custommethanol: 0.88 aqueous ammonia solution, and was then further purified by a second column
10. washeluting with 95:5, by volume, ethyl acetate