Reaction Steps
To a solution of methyl 1-(3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxamido)propanoyl)pyrrolidine-2-carboxylate (63 mg, 0.083 mmol) in Dioxane (2 mL) was added NaOH (1N) (0.417 mL, 0.417 mmol). The mixture was heated to 85° C. for 15 h, then cooled to rt and was diluted with 5 mL of 1N HCl and was extracted with dichloromethane (4×5 mL). The combined organic layers were dried with Na2SO4, the drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by Biotage flash chromatography using a 0-10% MeOH in DCM gradient with 0.1% HOAc then by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to give 1-(3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-carboxyphenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxamido)propanoyl)pyrrolidine-2-carboxylic acid (27.3 mg, 0.038 mmol, 45.0% yield) as a white solid. LCMS: m/e 726.4 (M−H)−, 2.36 min (method 4). 1H NMR (500 MHz, Acetic) δ ppm 8.03 (d, J=8.24 Hz, 2H), 7.30 (d, J=8.24 Hz, 2H), 5.37 (d, J=4.58 Hz, 1H), 4.78 (s, 1H), 4.64 (s, 1H), 4.57 (dd, J=8.70, 3.51 Hz, 1H), 3.52-3.75 (m, 4H), 3.09-3.20 (m, J=18.43, 11.08, 11.08, 4.27 Hz, 1H), 2.68-2.82 (m, 2H), 2.58 (td, J=12.36, 3.05 Hz, 1H), 1.73 (s, 3H), 1.07 (s, 6H), 1.05 (s, 3H), 1.03-2.53 (m, 25H), 1.01 (s, 3H), 0.99 (s, 3H).
