1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86659852, compound

Participants

Reaction Steps

The title compound is prepared by treating a solution of (3aR,4S,6aS)-4-methyl-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-amine from Example 27 (0.075 g, 0.263 mmol) in 1 mL dichloromethane with (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (0.067 g, 0.289 mmol) followed by of 1-hydroxybenzotriazole hydrate (0.044 g, 0.289 mmol). The reaction was stirred for 5 minutes, and then N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.051 mL, 0.289 mmol) was added to the reaction mixture followed by stirring at ambient temperature overnight. The reaction was quenched with saturated aqueous sodium bicarbonate, and the crude material was chromatographed using a 12 g silica gel cartridge eluted with 3%-100% ethyl acetate/hexanes over 30 minutes to give (2S,4R)-tert-butyl 4-fluoro-2-((3aR,4S,6aS)-4-methyl-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate which was treated with 4 N HCl in 1,4-dioxane (1 mL, 4.00 mmol). An oil slowly gummed out of solution. The reaction was stirred at room temperature for 18 hours, and the solvent was removed under a stream of nitrogen. The crude material was purified using a 12 g silica gel cartridge eluted with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.03 (bs, 1H), 7.52 (m, 1H), 7.00 (d, J=7.2, 1H), 6.55 (d, J=8.5, 1H), 5.22 (dt, J=54.3, 3.5, 1H), 4.22-4.14 (m, 1H), 3.75-3.45 (m, 4H), 3.41-3.27 (m, 2H), 3.22-3.12 (m, 1H), 3.02-2.74 (m, 2H), 2.58 (dddd, J=23.7, 15.0, 8.5, 2.3, 1H), 2.32-2.11 (m, 2H), 1.99 (dq, J=13.3, 8.7, 1H), 1.78 (dt, J=13.2, 8.7, 1H), 1.48 (s, 3H), 1.46-1.13 (m, 1H); MS (ESI+) m/z 401 (M+H)+.

Provenance & Evidence