Methanesulfonic Acid → HCID 178477846, compound

Participants

Reaction Steps

To a stirred solution of 8-Chloro-6,11-dihydro-11-(4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (9) (499 mg; 1.59 mmol) (disclosed in published application WO 95/10516, Apr. 20, 1995), ω-[1-(triphenylmethyl)-1H-imidazol-4-yl]-pentanal (6) (699 mg; ˜90% pure; 1.59 mmol) and methanesulfonic acid (0.10 mL; 1.59 mmol)) in anhydrous methanol (100 mL), was added anhydrous magnesium sulfate (380 mg) The resultant suspension was stirred at room temperature for 45 min. A 1.0M solution of sodium cyanoborohydride in tetrahydrofuran (1.12 mL; 1.12 mmol) was added and the resultant mixture stirred at room temperature for 22 h. The reaction mixture was filtered through Celite, and solvent evaporated under reduced pressure. The residue was dissolved in dichloromethane (25 mL) and washed successively with 1.1M sodium bicarbonate (15 mL) and water (2×10 mL). The organic layers were dried over anhydrous magnesium sulfate; filtered; solvent evaporated under reduced pressure and dried under high vacuum to obtain a pink glassy solid. The residual solid was chromatographed on silica gel, eluting with a gradient of 3.9M ammonia in methanol-dichloromethane (3:97→5:95), to obtain the imidazole-N-tritylated precursor of the title compound, which, after drying under high vacuum, was an off-white foam, mp 75-78° C. (melted to a viscous gum). FABMS: 451 (MH+; 20%); 243 (Ph3C+; 100%).

Provenance & Evidence