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-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

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 (251 mg; compound C10), TOTU (270 mg), HOAT (129 mg), DIPEA (327 mg) in DCM (8 ml) is stirred for 1 h at RT. To this mixture 1-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione trifluoroacetate (359 mg; compound B25) is added and the reaction mixture is stirred for additional 3 h at RT. Additional 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (125 mg; compound C10), TOTU (207 mg) and HOAT (86 mg) are added to drive the reaction to completion. After stirring for 1 h at RT the reaction is quenched by addition of DCM (10 ml) and a saturated aqueous solution of sodium bicarbonate (10 ml). The organic phase is separated and the aqueous phase is extracted with DCM (5 ml). The combined organic phases are applied to a phase separator and the solvent is removed under vacuum. The resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: cyclohexane/EtOAc, 100/0 to 0/100 (v/v)] to yield the title compound as a solid.

Provenance & Evidence