反应详情

A mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(2-methoxy-2-oxoethylamino)ethylcarbamoyl)-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 (50 mg, 0.071 mmol), iodoethane (0.047 mL, 0.571 mmol) and potassium carbonate (19.72 mg, 0.143 mmol) in acetonitrile (2.0 mL) and dioxane (2.0 mL) was heated up for 8 hours. LCMS indicated the formation of desired product and consumption of starting material. The reaction mixture was quenched with distilled water, extracted with DCM (3×3 mL). All the extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude intermediate methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(ethyl(2-methoxy-2-oxoethyl)amino)ethylcarbamoyl)-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. To this intermediate in dioxane (1 mL) was added 1N sodium hydroxide (0.224 mL, 0.224 mmol). The reaction mixture was heated up at 78° C. for 3 hours until LCMS indicated the consumption of starting material. The reaction mixture was filtered and the clear solution was purified by prep HPLC to provide the title compound as a white solid (29 mg, 59%). LCMS: m/e 687.40 (M+H)+, 2.11 min (method 1). 1H NMR (500 MHz, Acetic Acid-d4) 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), 4.65 (s, 1H), 4.02 (s, 2H), 3.85-3.63 (m, 2H), 3.58-3.37 (m, 4H), 3.22-3.01 (m, 1H), 2.69-2.43 (m, 1H), 1.73 (s, 3H), 2.30-1.20 (m, 24H), 1.08 (s, 3H), 1.07 (s., 3H), 1.06 (s., 3H), 1.01 (s, 3H), 0.99 (s, 3H).

1. temperaturewas heated up for 8 hours
2. customthe formation of desired product and consumption of starting material
3. customThe reaction mixture was quenched with distilled water
4. extractionextracted with DCM (3×3 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure