Reaction Steps
N-(tert-Butoxycarbonyl)-L-leucine (180 mg, 0.778 mmol), hydroxybenzotriazole (119 mg, 0.778 mmol), and (3aS,4R,6aR)-2-(3-(trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-amine (201 mg, 0.707 mmol) from Example 154 Step A were combined in dichloromethane (1 mL). After 20 minutes, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (0.138 mL, 0.778 mmol) was added and the reaction stirred at room temperature for 24 hours. The reaction was quenched with water, and the layers were separated. The aqueous layer extracted with 1 mL of dichloromethane. The combined organic layers were applied to a silica gel cartridge (Analogix®, Burlington, Wis., RS15-24) and eluted with 1-10% methanol (2 N ammonia)/dichloromethane to give N2-(tert-butyloxycarbonyl)-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.66 (d, J=7.1, 1H), 7.97 (d, J=8.5, 1H), 7.73 (s, 1H), 7.56 (s, 2H), 7.44 (t, J=7.7, 1H), 4.70 (dd, J=5.9, 11.0, 1H), 4.40 (br s, 1H), 3.56 (d, J=13.5, 1H), 3.41 (d, J=13.5, 1H), 2.74 (d, J=8.9, 1H), 2.48 (s, 2H), 2.37-2.31 (m, 1H), 2.27 (d, J=8.4, 1H), 2.24-2.19 (m, 1H), 2.12 (dq, J=6.0, 12.0, 1H), 1.91-1.81 (m, 4H), 1.66 (td, J=7.4, 14.7, 1H), 1.50 (s, 9H), 1.43-1.35 (m, 1H), 0.87 (d, J=5.9, 3H), 0.84 (d, J=5.6, 3H); MS (ESI+) m/z 498 (M+H)+.
