反应详情

To a suspension of 1-[(1-ethyl-1H-pyrazol-4-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (300 mg; compound B42), 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (253 mg; compound C10), EDCI (122 mg) and HOBT hydrate (86 mg) in DCM (10 ml) DIPEA (0.28 ml) is added. After 45 min additional 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (126 mg; compound C10) is added and the reaction mixture is stirred for 14 h at RT. Water and aqueous potassium hydrogen sulfate solution (10% w/w) are added and the mixture is extracted with DCM. The combined organic layers are dried (sodium sulfate) and concentrated under reduced pressure. The residue is purified by flash column chromatography [silica gel, eluation gradient: DCM/MeOH, 1/0 to 1/1 (v/v)] and preparative HPLC to afford the title compound as a solid.

1. additionis added
2. extractionthe mixture is extracted with DCM
3. dry with materialThe combined organic layers are dried (sodium sulfate)
4. concentrationconcentrated under reduced pressure
5. customThe residue is purified by flash column chromatography [silica gel, eluation gradient: DCM/MeOH, 1/0 to 1/1 (v/v)] and preparative HPLC