Reaction Steps
To a solution of 4-[(1S,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]benzoate, TFA (24.3 mg, 0.029 mmol) in THF (3 mL) was added a 0.753 molar aqueous solution of lithium hydroxide monohydrate (0.232 mL, 0.116 mmol). The reaction mixture was heated to 75° C. After 5.5 h, the reaction mixture was concentrated to dryness. The crude residue was dissolved in THF (1.2 mL), MeOH (0.3 mL) and 1N HCl (0.2 mL). The resulting solution was filtered and purified using prep HPLC method 3 to give 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, TFA (16.5 mg, 0.020 mmol, 69.1% yield) as a white solid. LCMS: m/z 709.6 (M+H+), retention time 2.072 min (method 6). 1H NMR (500 MHz, METHANOL-d4) δ=7.91 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 7.11 (s, 1H), 3.25-3.20 (m, 6H), 3.17 (d, J=5.5 Hz, 4H), 2.65-2.59 (m, 1H), 2.44 (dd, J=2.7, 13.1 Hz, 1H), 2.37 (dd, J=7.0, 12.5 Hz, 1H), 2.19-2.04 (m, 1H), 1.98-1.89 (m, 1H), 1.85 (d, J=13.1 Hz, 1H), 1.74 (dd, J=3.7, 7.9 Hz, 2H), 1.71-1.60 (m, 3H), 1.56-1.45 (m, 8H), 1.44-1.37 (m, 4H), 1.36-1.25 (m, 2H), 1.16-1.09 (m, 2H), 1.05 (s, 3H), 1.04 (s, 3H), 1.00 (s, 3H), 0.95 (d, J=2.1 Hz, 1H), 0.91 (d, J=6.7 Hz, 3H), 0.81 (d, J=6.7 Hz, 3H), 0.78 (s, 3H), 0.72 (s, 3H).
