反应详情

温度

120 °C

A mixture of 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazole]-4″(3″H)-thione (Example 29 Step 3, 365 mg, 0.92 mmol) and 7M ammonia in MeOH (10 mL, 70.00 mmol) was prepared in a microwave vial. The vial was sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was concentrated and the residue was dissolved in 7M ammonia in McOH (4 mL) and heated once more at 120° C. for 30 min using MW. Again, the mixture was concentrated, 7M ammonia in MeOH (10 mL, 70.00 mmol) was added and the mixture was heated at 120° C. The mixture was concentrated and the crude product was dissolved in 20% MeOH in DCM and filtered through a silica pad and eluted with 20% MeOH in DCM. After concentration of the organic layer, DCM was added to the residue. A solid was formed which was filtered off and washed with DCM, yielding 94 mg of the title compound (27% yield). The mother liquor was concentrated, Et2O was added and the solid was filtered off and dried, yielding a second crop of the title compound (85 mg, 24% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.19 (d, 1H), 1.43 (m, 3H), 1.80 (d, 2H), 1.95 (m, 2H), 2.20 (s, 3H), 3.07 (d, 1H), 3.21 (s, 3H), 6.68 (d, 1H), 6.74 (br. s., 2H), 6.87 (d, 1H), 7.31 (dd, 1H); MS (ES+) m/z 379 [M+H]+.

1. customwas prepared in a microwave vial
2. customThe vial was sealed
3. concentrationThe mixture was concentrated
4. dissolutionthe residue was dissolved in 7M ammonia in McOH (4 mL)
5. temperatureheated once more at 120° C. for 30 min
6. concentrationAgain, the mixture was concentrated
7. temperaturethe mixture was heated at 120° C
8. concentrationThe mixture was concentrated
9. dissolutionthe crude product was dissolved in 20% MeOH in DCM
10. filtrationfiltered through a silica pad
11. washeluted with 20% MeOH in DCM
12. additionAfter concentration of the organic layer, DCM was added to the residue
13. customA solid was formed which
14. filtrationwas filtered off
15. washwashed with DCM