To a stirred solution of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (119 mg, 0.358 mmol), EDC (82 mg, 0.430 mmol) and HOBT (58 mg, 0.430 mmol) in DMF (3 mL) at room temperature under nitrogen was added a mixture of 9-methyl-3-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a][1,4]diazepine hydrochloride from Step G (90 mg, 0.351 mmol) and triethylamine in DMF (3 mL). The resultant mixture was stirred at ambient temperature for 4 days. Then the reaction mixture was diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by preparative thin layer chromatography (5% of 10% methanolic ammonium hydroxide in dichloromethane) to yield the N-BOC precursors of the title compound as a mixture of diastereomers. Chiral HPLC separation (ChiralCel OD column, 6% ethanol/hexane) provided the individual diastereomers, each of which was treated with 4 N hydrogen chloride in dioxane at ambient temperature for 2 h. Concentration gave the individual diastereomers of the title compound. Faster eluting diastereomer: MS 436.0 (M+1); slower eluting diastereomer: MS 436.0 (M+1).
