反应详情

N-(3,4-Dichlorophenyl)piperazine-1-carboxamide hydrochloride (251 mg) and (2R)-1-(tert-Butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid (200 mg) were dissolved in dry THF (10 mL) followed by addition of N,N-di-isopropylethylamine (0.26 ml) and HATU (335 mg) and the reaction was stirred for 4 h. A further 0.26 ml of N,N-di-iso-propylamine was added and the reaction was stirred for 18 h at rt. The solvent was evaporated under reduced pressure then redissolved in dichloromethane (50 ml) followed by washing with sat. aqueous NaHCO3 (20 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (3-10% methanol:dichloromethane) afforded the crude product (180 mg) as a foam which was used without further purification. The foam was then dissolved in TFA/DCM (1:1, 10 ml) and stirred for 30 mins. The solvent was removed under reduced pressure then taken up in 1M. aqueous sodium hydroxide (30 ml) and extracted with dichloromethane (2×30 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (5-25% MeOH:DCM) afforded the title compound (95 mg) as a white foam.

1. stirringthe reaction was stirred for 18 h at rt
2. customThe solvent was evaporated under reduced pressure
3. dissolutionthen redissolved in dichloromethane (50 ml)
4. washby washing with sat. aqueous NaHCO3 (20 ml)
5. customThe organic layer was separated on a phase separation cartridge
6. customevaporated
7. customPurification by chromatography (3-10% methanol:dichloromethane)
8. customafforded the crude product (180 mg) as a foam which
9. customwas used without further purification
10. dissolutionThe foam was then dissolved in TFA/DCM (1:1, 10 ml)
11. stirringstirred for 30 mins
12. customThe solvent was removed under reduced pressure
13. extractionaqueous sodium hydroxide (30 ml) and extracted with dichloromethane (2×30 ml)
14. customThe organic layer was separated on a phase separation cartridge
15. customevaporated
16. customPurification by chromatography (5-25% MeOH:DCM)