反应详情

1-(tert-Butoxycarbonyl)-piperidine4-carboxylic acid (3.2 g) in dry DMF (30 ml) was treated first with EDC (5.4 g) and catalytic HOAt followed by (S)-1-isopropyl-2-methyl piperazine hydrochloride (D27)(2 g) and N,N-diisopropylethylamine (5 ml). After the reaction mixture was stirred overnight, water (50 ml) was added and the cloudy precipitate was extracted into EtOAc (2×25 ml), dried (MgSO4) and filtered. The filtrate was absorbed on silica and purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. The fractions containing the required product were evaporated to give the title compound (D28) as an oil (3.8 g). LCMS electrospray (+ve) 354 (MH+).

1. extractionthe cloudy precipitate was extracted into EtOAc (2×25 ml)
2. dry with materialdried (MgSO4)
3. filtrationfiltered
4. customThe filtrate was absorbed on silica
5. custompurified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]
6. additionThe fractions containing the required product
7. customwere evaporated