Reaktionsschritte
To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-thioureido-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 (150 mg, 0.249 mmol) in DMF (3 mL) was added N,N-diisopropylethylamine (0.217 mL, 1.244 mmol) and 2-bromo-1-(thiophen-3-yl)ethanone (77 mg, 0.373 mmol). The reaction mixture was stirred at rt overnight. After 18 h, the reaction mixture was poured into a separatory funnel containing H2O (5 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to white solid. The material was redissolved in DCM (3 mL). MeOH was added and the mixture was concentrated to remove most of DCM. The resulting white precipitate was filtered, washed with cold MeOH, and dried in a vacuum oven to give a 4:1 mixture of (as determined by HPLC integration) methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(4-(thiophen-3-yl)thiazol-2-ylamino)-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 and methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-oxo-2-(thiophen-3-yl)ethyl)(4-(thiophen-3-yl)thiazol-2-yl)amino)-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 (134 mg, 82% yield) as white solid. LC/MS: m/e 709.3 (M+H)+, 3.62 min and m/e 833.3 (M+H)+, 2.63 min (method 9), respectively. Reverse phased analytical HPLC showed ratio of major product with rt=16.04 min (m/e 709.3 (M+H)+) to minor product with rt=15.42 min (m/e 833.3 (M+H)+) product of 80%:20% (using analytical HPLC method 2).
