HOAt → HCID 53246869, compound

Participants

Reaction Steps

A solution of 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (199 mg; compound C10), TOTU (213 mg) and HOAT (102 mg) in DIPEA (259 mg) is stirred for 50 min at RT. Subsequently, 1-[(2-methyl-1,3-thiazol-5-yl)methyl]-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione trifluoroacetate (276 mg; compound B44) is added and the reaction mixture is stirred for additional 60 min at RT. The solvent is removed under reduced pressure and to the resulting residue DCM (15 ml) and saturated aqueous sodium bicarbonate solution (3 ml) are added. The organic phase is separated and the aqueous phase is extracted with DCM (10 ml). The combined organic phases are applied to a phase separator, dried over magnesium sulfate and the solvent is removed under reduced pressure to give the crude title compound. The residue is first purified by flash chromatography [amino phase silica gel, eluation gradient: cyclohexane/EtOAc, 100/0 to 0/100 (v/v)]. After a second purification step applying preparative TLC [20×20 cm TLC plates with 0.5 mm thickness, eluent: EtOAc/triethylamine, 97/3 (v/v)] the title compound is obtained as a solid.

Provenance & Evidence