反应详情

To a mixture of 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (99.4 mg; compound C10), 1-(3-Ethyl-[1,2,4]oxadiazol-5-ylmethyl)-6-phenyl-3-piperidin-4-yl-1H-thieno[3,2-d]pyrimidine-2,4-dione (109 mg; compound B52) and HOBT (38 mg) in DCM (2.5 ml) is added EDCI (48.9 mg). The mixture is stirred for 2.5 h at RT. EtOAc (25 ml) is added and the mixture is extracted with 1 M aqueous hydrochloride solution (5 ml) (three times). The combined aqueous phases are washed with EtOAc (15 ml) and subsequently the combined organic phases are washed with water (5 ml) (three times) and afterwards with saturated solution of sodium bicarbonate (10 ml) (three times). The organic phase is dried over magnesium sulfate, concentrated in vacuo and the resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: EtOAc/cyclohexane=0/100 to 20/80 (v/v)] to give the title compound as a solid.

1. extractionthe mixture is extracted with 1 M aqueous hydrochloride solution (5 ml) (three times)
2. washThe combined aqueous phases are washed with EtOAc (15 ml)
3. washsubsequently the combined organic phases are washed with water (5 ml) (three times) and afterwards with saturated solution of sodium bicarbonate (10 ml) (three times)
4. dry with materialThe organic phase is dried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. customthe resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: EtOAc/cyclohexane=0/100 to 20/80 (v/v)]