Reaction Steps
(3aR,4S,6aS)-2-(6-(Trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-amine from Example 264 Step A (95.7 mg, 0.353 mmol) was combined with (S)-2-(tert-butoxycarbonyl(methyl)amino)-4,4-dimethylpentanoic acid (101 mg, 0.388 mmol) and 1-hydroxybenzotriazole hydrate (59.4 mg, 0.388 mmol) in dichloromethane (1 mL). After 20 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.068 mL, 0.388 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with 2×2 mL of dichloromethane. The combined extracts were applied directly to a 12 g silica gel cartridge and purified with a gradient of 1-10% methanol in (2 N ammonia)/dichloromethane. The resulting oil was treated with 4 N hydrogen chloride in 1,4-dioxane (1 mL, 4 mmol) for 3 hours at room temperature. The solvent was removed under a stream of nitrogen and the residue basified with aqueous sodium bicarbonate and extracted with 2×2 mL of dichloromethane. The combined extracts were applied directly to a 12 g silica gel cartridge and purified with a gradient of 1-10% methanol in (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.36 (d, J=7.3, 1H), 7.51 (t, J=7.9, 1H), 6.98 (d, J=7.2, 1H), 6.52 (d, J=8.6, 1H), 4.45-4.35 (m, 1H), 3.74 (dd, J=10.9, 2.8, 1H), 3.62 (dd, J=10.8, 7.5, 1H), 3.52 (dd, J=10.7, 7.8, 1H), 3.29 (dd, J=10.8, 3.4, 1H), 3.24-3.18 (m, 1H), 2.79-2.64 (m, 2H), 2.42 (s, 3H), 2.14 (td, J=12.5, 7.0, 1H), 2.01-1.79 (m, 3H), 1.69 (dq, J=12.8, 8.0, 1H), 1.51 (dd, J=14.1, 6.6, 1H), 1.44-1.33 (m, 1H), 1.00 (s, 9H); MS (ESI+) m/z 413 (M+H)+.
