反应详情

To a mixture of 5-cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid (INTERMEDIATE 25, 710 mg, 1.51 mmol) in THF (11.2 mL) is added 1,1′-carbonyldiimidazole (270 mg, 1.66 mol) and the reaction mixture is stirred 90 min at room temp. The reaction mixture is cooled to 5° C. and a solution of sodium borohydride (85 mg, 2.27 mmol) in water (1.4 mL) is added dropwise. After stirring at room temp. for 3 h, the reaction mixture is acidified with dilute aqueous acetic acid, diluted with water and extracted with ethyl acetate. The organic phase is washed with water, dried over MgSO4 and concentrated under reduced pressure. The crude product is purified by reversed phase HPLC. Yield: 420 mg; ESI mass spectrum [M+H]+=456; Retention time HPLC: 0.62 min (X012_S02).

1. temperatureThe reaction mixture is cooled to 5° C.
2. stirringAfter stirring at room temp. for 3 h
3. extractionextracted with ethyl acetate
4. washThe organic phase is washed with water
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe crude product is purified by reversed phase HPLC
8. custom0.62 min (X012_S02)