Reaction Steps
To a flask containing (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-carboxylic acid (0.1 g, 0.175 mmol) was added oxalyl chloride (2M in DCM) (3 mL, 6.00 mmol). The mixture bubbled vigorously for several minutes, then bubbling ceased and the clear solution was stirred at rt for 3 h. The mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane and concentrated two additional times. The crude product was diluted with DCE (2 mL) and Hunig'sBase (0.152 mL, 0.873 mmol) and N-(3-aminopropyl)-N-methylcarbamic acid tert-butyl ester (0.061 g, 0.324 mmol) were added to the mixture. After stirring the mixture for 19 h at rt, the mixture was diluted with 10 mL of water and was extracted with dichloromethane (3×10 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 0-5% MeOH in DCM gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(tert-butoxycarbonyl(methyl)amino)propylcarbamoyl)-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)benzoate (122 mg, 0.164 mmol, 94% yield) as a white foam. LCMS: m/e 741.6 (M−H)−, 3.41 min (method 3). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.90 (d, J=8.24 Hz, 2H), 7.17 (d, J=8.24 Hz, 2H), 6.89 (br. s., 1H), 5.26 (d, J=4.58 Hz, 1H), 4.74 (d, J=1.83 Hz, 1H), 4.57 (s, 1H), 3.88 (s, 3H), 3.40-3.04 (m, 5H), 2.81 (s, 3H), 2.51 (t, J=10.83 Hz, 1H), 2.19-2.04 (m, 2H), 1.99-1.87 (m, 1H), 1.68 (s, 3H), 1.45 (s, 9H), 0.98 (s, 3H), 1.52-0.95 (m, 20H), 0.97 (s, 3H), 0.94 (s, 3H), 0.90 (s, 6H).
