反应详情

Isopropylisocyanate (0.029 ml) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide (105 mg) [see Example 8] and potassium carbonate (37.5 mg) in acetonitrile (3 ml). The reaction mixture was stirred at room temperature for 5 hours, after which time the solvent was removed under reduced pressure and the residue 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 gradient of 94.6:5.6:0.8 changing to 93:7:1, by volume, dichloromethane:methanol: 0.88 aqueous ammonia solution to afford (cis)-4-[2-([(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinyl]carbonylamino)ethyl]-N1-isopropyl-3,5-dimethyl-1-piperazinecarboxamide (72.8 mg) as a white solid.

1. customafter which time the solvent was removed under reduced pressure
2. customthe residue partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. dry with materialdried over magnesium sulphate
5. customthe solvent removed under reduced pressure
6. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 94.6:5.6:0.8 changing to 93:7:1, by volume, dichloromethane