1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 66997255, compound

Participants

Reaction Steps

To a solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (2.87 g, 12.31 mmol) and (3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine from Example 33 Step A (2.93 g, 13.54 mmol) in dichloromethane (16.97 mL) was added 1-hydroxybenzotriazole hydrate (2.073 g, 13.54 mmol). After 2 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (2.388 mL, 13.54 mmol) was added and the reaction was stirred at ambient temperature overnight. The reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The solvent was removed in vacuo. The crude material was purified using an 80 g silica gel cartridge eluted with a gradient of 0-5% methanol (2 N ammonia)/dichloromethane over 20 minutes to give (2S,4R)-tert-butyl 2-((3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)-4-fluoropyrrolidine-1-carboxylate: 1H NMR (400 MHz, pyridine-d5) δ ppm 7.70 (s, 1H), 7.38-7.36 (m, 2H), 7.33-7.26 (m, 2H), 7.24-7.17 (m, 1H), 5.19 (dd, J=53.5, 3.3, 1H), 4.59 (t, J=7.8, 1H), 4.31-4.22 (m, 1H), 4.04-3.92 (m, 1H), 3.68 (dd, J=12.9, 3.7, 1H), 3.62-3.57 (m, 1H), 3.60-3.45 (m, 2H), 2.83-2.76 (m, 1H), 2.56-2.58 (m, 1H), 2.52-2.43 (m, 3H), 2.35 (m, 3H), 2.10 (dq, J=12.5, 6.3, 1H), 1.92-1.82 (m, 1H), 1.67-1.57 (m, 1H), 1.49 (s, 9H), 1.46-1.36 (m, 1H); MS (ESI+) m/z 432 (M+H)+.

Provenance & Evidence