反应详情

A solution of 0.070 g (0.20 mmol) of 3-[(S)-4-(3,4-dichloro-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-propionic acid (intermediate 12) in 1.5 ml of DMF was treated with 0.045 ml (0.28 mmol) of (S)-6-aza-spiro[2.5]octan-4-ol; hydrochloride (intermediate 2), 0.054 ml (0.40 mmol) of triethylamine and at 0° C. with 0.081 g (0.22 mmol) of HATU. Over night, the suspension was naturally warmed to RT, poured on aqueous 10% KHSO4 solution and extracted with EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl, dried (Na2SO4) and evaporated to give after purification with flash chromatography (SiO2, dichloromethane/methanol 99:1 to 96:4) 0.069 g (70%) of the titled compound as white foam. MS: 483.2 (MH+, 2Cl).

1. customat 0° C.
2. waitOver night
3. extractionextracted with EtOAc (3×)
4. washThe organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl
5. dry with materialdried (Na2SO4)
6. customevaporated
7. customto give
8. customafter purification with flash chromatography (SiO2, dichloromethane/methanol 99:1 to 96:4) 0.069 g (70%) of the titled compound as white foam