反应详情

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 1-bromopinacolone (0.056 mL, 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 wash added and concentrated to remove most of the DCM. The resulting white precipitate was filtered, washed with cold MeOH, and dried in a vacuum oven to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(4-tert-butylthiazol-2-ylamino)-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 (154.0 mg, 0.225 mmol, 91% yield) as a white solid. LC/MS: m/e 683.4 (M+H)+, 2.88 min (method 11). 1H NMR (500 MHz, CHLOROFORM-d) δ 7.95 (d, J=8.2 Hz, 2H), 7.22 (d, J=8.2 Hz, 2H), 6.06 (s, 1H), 5.31 (d, J=4.6 Hz, 1H), 4.88 (s, 1H), 4.77 (s, 1H), 4.66 (s, 1H), 3.93 (s, 3H), 2.72 (d, J=13.7 Hz, 1H), 2.68-2.62 (m, 1H), 2.55 (dd, J=8.1, 12.7 Hz, 1H), 2.13 (dd, J=6.4, 17.1 Hz, 1H), 2.07-1.98 (m, 1H), 1.92-1.83 (m, 1H), 1.82-1.76 (m, 1H), 1.74 (s, 3H), 1.73-1.66 (m, 2H), 1.61 (s, 1H), 1.57-1.49 (m, 3H), 1.49-1.40 (m, 4H), 1.40-1.31 (m, 3H), 1.29 (s, 9H), 1.27-1.21 (m, 1H), 1.18-1.12 (m, 1H), 1.10 (s, 3H), 1.04 (s, 3H), 1.01 (s, 3H), 0.95 (s, 6H).

1. waitAfter 18 h
2. additionthe reaction mixture was poured into a separatory funnel
3. extractionextracted with EtOAc (50 mL)
4. washThe organic layer was washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated to white solid
8. dissolutionThe material was redissolved in DCM (3 mL)
9. washMeOH wash
10. additionadded
11. concentrationconcentrated
12. customto remove most of the DCM
13. filtrationThe resulting white precipitate was filtered
14. washwashed with cold MeOH
15. customdried in a vacuum oven