4-Pyridinecarboxylic acid, 1-oxide → 1-(8-CHLORO-5,11-DIHYDRO[1]BENZOTHIEPINO[4,3-b]PYRIDIN-11-YL)-4-(4-PYRIDINYLCARBONYL)PIPERAZINE N4-OXIDE

Participants

Reaction Steps

To a stirred suspension of 8-chloro-5,11-dihydro-11-(1-piperazinyl)[1]benzothiepino[4,3-b]pyridine (251 mg, 0.762 mmol) and isonicotinic acid N-oxide (128 mg, 0.918 mmol) in dry dichloromethane (20 mL), add 1-hydroxybenzotriazole hydrate (123 mg, 0.909 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (175 mg, 0.912 mmol). Stir the resultant mixture at room temperature for 3 hours. Wash the reaction mixture successively with 2.5M aqueous sodium hydroxide (5 mL), water (4×10 mL), and brine (15 mL). Dry the washed solution over anhydrous magnesium sulfate, filter out the drying agent, and remove solvent from the filtrate under reduced pressure. Flash chromatograph the residue on silica gel, eluting with methanol/dichloromethane (1:9) to obtain the title compound as a 3/4 hydrate (240 mg, 70% yield): mp 162°-165.5° C. (melts to a viscous gum); MS (FAB) m/z 450 [M+ +1].

Provenance & Evidence