Diisopropylethylamine → 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-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a suspension of 1-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-6-phenyl-3-piperidin-4-ylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (200 mg; compound B27), 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (188 mg; compound C10) and HBTU (196 mg) in DCM (7.5 ml) is added DIPEA (0.33 ml). The reaction mixture is stirred at RT for 14 h. Additional DCM (10 ml) and saturated aqueous sodium bicarbonate solution (10 ml) are added and the mixture is filtered using a phase separator. The organic layer is concentrated under reduced pressure and the residue is purified by flash column chromatography [silica gel, eluation gradient: DCM/MeOH, 1/0 to 1/1 (v/v)] followed by preparative HPLC to yield the title compound as a solid.

Provenance & Evidence