反应详情

A suspension of 0.035 g (0.10 mmol) of 4-[(S)-4-(3-chloro-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-butyric acid (intermediate 19) and 0.012 g (0.11 mmol) N-hydroxy-2-pyridon in 1.5 ml of DMF was treated at 0° C. with 0.021 g (0.11 mmol) of EDCI and was naturally warmed to RT over night. A solution of 0.035 g (0.10 mmol) of 2-oxa-7-aza-spiro[3.5]nonane trifluoro-acetic acid salt (1:2) (intermediate 20) and 0.030 ml (0.30 mmol) of triethylamine in 1.5 ml of DMF was then added and the reaction was stirred for 1 h at RT. The solution was poured on aqueous 10% KHSO4 solution and extracted with Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.013 g of the titled compound with maximal 60% purity. The aqueous phases were reextracted with EtOAc (3×), the organic phases were dried (NaSO4), evaporated and dried under reduced pressure to give 0.029 g (62%) of the titled compound as light yellow foam. MS: 463.21 (MH+, Cl).

1. extractionextracted with Et2O (3×)
2. washThe organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl
3. dry with materialdried (Na2SO4)
4. customevaporated