Hydrochloric Acid → HCID 59003127, compound

Participants

Reaction Conditions

Reaction Steps

Add 3,5-bis(trifluoromethyl)benzylamine (23 mg, 0.095 mmol) followed by titanium isopropoxide (0.035 mL, 0.12 mmol) to isopropyl 6-fluoro-7-methyl-5-oxo-2,3,4,5-tetrahydro benzo[b]azepine-1-carboxylate (24 mg, 0.086 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 2 days. Filter the residue over silica cartridge, eluting with hexanes/ethyl acetate (8:1) to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-7-methyl-2,3-dihydro-benzo[b]azepine-1-carboxylic (34 mg, 79%). Add methanol (1 mL) and platinum oxide (2 mg, 0.007 mmol) and hydrogenate the mixture at 1 atmosphere and room temperature for 7 h. Filter through celite and remove the solvent under reduced pressure to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-7-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (36 mg, quantitative). Add acetic anhydride (0.1 mL, 1.07 mmol) dropwise to a suspension of the amine (36 mg, 0.071 mmol) and pyridine (0.1 mL g, 1.07 mmol) in dichloromethane (0.5 mL) under nitrogen cooled to 0° C. After the addition is complete, remove the cooling bath and warm the reaction to room temperature and stir for 12 h. Add 1 N hydrochloric acid and extract with dichloromethane (3×10 mL). Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Chromatograph the residue over silica cartridge, eluting with hexanes/ethyl:acetate (6:1), to afford the title compound (18 mg, 46%); MS (ES+): 549 (M+H)

Provenance & Evidence