Reaction Steps
N-(tert-Butoxycarbonyl)-D-leucine (72.7 mg, 0.314 mmol), 2,2-dicyclohexyl-N-[(3aS,4R,6aR)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide (95 mg, 0.286 mmol) from Example 74, and hydroxybenzotriazole (48.1 mg, 0.314 mmol) were combined in dichloromethane (10 mL). After 20 minutes, N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (0.056 mL, 0.314 mmol) was added, and the reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with water. The separated organic layer was reduced in volume, and the crude material was applied to a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) and eluted first with 10% to 100% ethyl acetate/hexanes and then with 1-10% methanol (2 N ammonia)/dichloromethane to give tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.26 (dd, J=7.2, 24.0, 1H), 7.91 (d, J=8.6, 1H), 4.48-4.36 (m, 1H), 4.12-3.96 (m, 1H), 3.87 (dd, J=7.4, 10.3, 1H), 3.70 (ddd, J=8.0, 14.4, 23.7, 1H), 3.40 (dd, J=5.7, 12.3, 1H), 2.77 (s, 1H), 2.58 (d, J=6.1, 1H), 2.08 (s, 1H), 2.01 (dd, J=5.6, 10.4, 2H), 1.96-1.55 (m, 17H), 1.54-1.50 (m, 9H), 1.49-1.37 (m, 2H), 1.19 (qdd, J=12.3, 22.3, 24.7, 11H), 1.00 (t, J=6.6, 3H), 0.88 (d, J=6.6, 1H).
