Diisopropylethylamine → 3-[1-({4-[(4aR,10bR)-8,9-dimethoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

To a suspension of 1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (190 mg, compound B39), 4-[(4aR,10bR)-8,9-dimethoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (220 mg; compound C16) and HBTU (167 mg) in DCM (4.0 ml) is added DIPEA (0.28 ml). The reaction mixture is stirred at RT for 1 h. Saturated aqueous sodium bicarbonate solution (2 ml) is 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 [amino phase silica gel, eluent: EtOAc] and subsequently by preparative HPLC and preparative TLC [20×20 cm TLC plates with 0.5 mm thickness, eluent: EtOAc/MeOH/triethylamine, 91/5/4 (v/v/v)] to yield the title compound as a solid.

Provenance & Evidence