Reaction Steps
The title compound was prepared by combining (3aR,4R,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-yl-4-bromobenzenesulfonate from Step 4 (150 mg, 0.305 mmol) and (S)-2-amino-4-methylpentanamide (119 mg, 0.916 mmol) in acetonitrile (0.2 mL). The reaction mixture was heated at 85° C. for 3 days, and the acetonitrile was evaporated. This material was purified using a 12 g silica gel cartridge eluted with a gradient of 0-3% methanol (2 N ammonia)/dichloromethane over 20 minutes to give crude product. It was further purified on 2×0.25 mm thin-layer chromatography plate eluted with 45% methanol (2 N ammonia)/dichloromethane to give N2-{(3aR,4S,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.25 (s, 1H), 7.99 (s, 1H), 7.52 (t, J=7.9, 1H), 6.98 (d, J=7.2, 1H), 6.49 (d, J=8.6, 1H), 3.60 (dd, J=10.6, 9.0, 1H), 3.55-3.40 (m, 3H), 3.24 (dd, J=10.8, 3.7, 1H), 3.17 (dd, J=10.2, 5.7, 1H), 2.83-2.71 (m, 1H), 2.64-2.55 (m, 1H), 2.30-2.10 (bs, 1H) 2.08-1.93 (m, 3H), 1.76 (ddd, J=13.5, 8.1, 5.5, 1H), 1.71-1.64 (m, 1H), 1.58 (dd, J=12.7, 5.8, 1H), 1.31 (dd, J=12.7, 5.9, 1H), 0.96 (d, J=6.6, 3H), 0.93 (d, J=6.6, 3H); MS (ESI+) m/z 385 (M+H)+.
