1-Hydroxybenzotriazole → N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepine-4-carboxamide

Participants

Reaction Steps

To a solution of 7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (177 mg; purity: about 50%) and 1-hydroxybenzotriazole (HOBt) (90 mg) in DMF (5 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (WSC) (127 mg), and the mixture was stirred for 1 hour. To the mixture were added a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline (107 mg) and triethylamine (0.12 ml) in DMF (5 ml) and a piece of 4-dimethylaminopyridine, and the mixture was stirred for 64 hours. The mixture was concentrated under reduced pressure, and to the residue was added water. The mixture was extracted with dichloromethane, and the organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with column chromatography (ethanol/ethyl acetate=1:1) and recrystallized from ethanol/diethylether to give yellow crystals of N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 1) (31.6 mg).

Provenance & Evidence