1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-(1,3-benzodioxol-5-yl)-3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a solution of 6-(1,3-benzodioxol-5-yl)-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (232 mg; compound B86) and 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (191 mg; compound C10) in DMF (10 ml) is added HOBt (74 mg) and EDCI (92 mg) and the reaction mixture is stirred at RT for 48 h. One additional equivalent of EDCI (92 mg) is added in order to complete the reaction. The reaction mixture is extracted for three times with DCM/H2O/saturated sodium chloride solution (150 ml/100 ml/35 ml). The organic phase is separated and dried with Na2SO4. After filtration and evaporation of all volatiles the resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: DCM/ethanol, 100/0/to 95/5 (v/v)] and by preparative HPLC to give the title compound as a solid.

Provenance & Evidence