HCID 86616080, compound → HCID 86616079, compound

Participants

Reaction Steps

Inject titanium isopropoxide (1.3 mL, 4.32 mmol) to a mixture of 6-fluor-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (572 mg, 2.16 mmol) and 3,5-bis(trifluoromethyl)benzylamine (972 mg, 3.2 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3-dihydro-benzo[b]azepine-1-carboxylic isopropyl ester (820 mg, 77%). Add methanol (9.3 mL) and platinum oxide (37 mg, 0.16 mmol) to 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3-dihydro-benzo[b]azepine-1-carboxylic isopropyl ester (742 mg, 1.5 mmol) and hydrogenate the mixture at 1 atmosphere and room temperature for 2 h. Filter through celite and remove the solvent under reduced pressure to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (730 mg, quantitative). Add acetic anhydride (0.5 mL, 5.78 mmol) dropwise to a suspension of the amine (190 mg, 0.385 mmol) and pyridine (0.5 mL, 5.78 mmol) in dichloromethane (1.5 mL), stir under nitrogen at room temperature for 14 h. Add 1 M hydrochloric acid and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (141 mg, 68%); MS (ES+): 535 (M+H).

Provenance & Evidence