Reaction Steps
To a solution of (1R,5S)-tert-butyl 3-(2-(((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]chrysen-3a-yl)amino)ethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate, 2 TFA (30 mg, 0.030 mmol) in THF (0.75 mL) and MeOH (0.25 mL) was added a solution of lithium hydroxide (1N) (0.148 mL, 0.148 mmol). The reaction mixture was stirred at 75° C. After 1 h, the reaction mixture was cooled to rt and purified by reverse phase prep-HPLC using HPLC method 7 and dried to give 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1R,5S)-8-(tert-butoxycarbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)ethyl)amino)-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]chrysen-9-yl)benzoic acid, 2 TFA (22.2 mg, 0.021 mmol, 69.0% yield) as pale yellow solid. LC/MS: m/e 768.8 (M+H)+, 2.34 min (method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.96 (d, J=8.1 Hz, 2H), 7.21 (d, J=8.3 Hz, 2H), 5.13 (d, J=5.4 Hz, 1H), 4.84 (br. s., 1H), 4.68 (s, 1H), 4.36 (br. s., 2H), 3.68-3.32 (m, 6H), 2.98 (d, J=10.3 Hz, 2H), 2.70 (br. s., 1H), 2.08 (br. s., 7H), 1.97-1.82 (m, 2H), 1.70 (d, J=5.9 Hz, 1H), 1.66 (s, 3H), 1.63-1.51 (m, 5H), 1.49 (s, 9H), 1.47-1.39 (m, 5H), 1.39-1.27 (m, 4H), 1.27-1.15 (m, 3H), 1.11 (s, 3H), 1.02 (s, 3H), 0.98 (s, 3H), 0.97-0.94 (m, 3H), 0.89 (s, 4H).
