反应详情

温度

100 °C

To a 20 mL microwave vial containing a mixture of 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.25 g, 0.564 mmol), benzophenone imine (0.142 mL, 0.846 mmol) and Cs2CO3 (0.735 g, 2.256 mmol) was added 1,4-dioxane (5 mL) and the suspension stirred with degassing under N2 for 5 min. Next added Xantphos (0.098 g, 0.169 mmol), degassed for 5 min, and then added Pd2(dba)3 (0.077 g, 0.085 mmol) and degassed for 1 min. The reaction vial was sealed and the mixture heated at 100° C. (heat block) with stirring for 2 h. The contents were cooled to RT, diluted with water (80 mL), and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered through Celite, and concentrated in vacuo. The crude solid was dissolved in THF (5 mL) and treated with HCl (0.564 mL, 1.692 mmol). The volatiles were removed in vacuo. The residue was dried under hi-vacuum, and then dissolved in MeOH/DCM followed by addition of silica gel. The contents were concentrated to dryness and dried under hi-vacuum for 1 h. The contents were purified by silica gel chromatography (dry loaded, eluent: 3-95% gradient chloroform (containing 10% 2M ammonia in methanol) and DCM). The collected solid was triturated from hot acetonitrile, and then placed in freezer for 15 min. The contents were filtered cold and washed with additional acetonitrile. The title compound was collected as 90 mg (41%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.72 (m, 2H), 1.78-1.89 (m, 2H), 1.91-2.00 (m, 2H), 2.01-2.10 (m, 2H), 2.12 (s, 3H), 2.22 (s, 3H), 4.32 (d, J=5.05 Hz, 2H), 4.84 (t, J=7.07 Hz, 1H), 5.41 (s, 2H), 5.88 (s, 1H), 6.65 (s, 1H), 6.88 (d, J=1.52 Hz, 1H), 7.95 (s, 1H), 8.14 (t, J=5.18 Hz, 1H), 11.53 (s, 1H); LC-MS (ES) m/z=379.2 [M+H]

1. additionTo a 20 mL microwave vial containing
2. customwith degassing under N2 for 5 min
3. customdegassed for 5 min
4. customThe reaction vial was sealed
5. temperature(heat block)
6. stirringwith stirring for 2 h
7. temperatureThe contents were cooled to RT
8. extractionextracted with EtOAc (2×)
9. dry with materialThe combined organic layers were dried over MgSO4
10. filtrationfiltered through Celite
11. concentrationconcentrated in vacuo
12. dissolutionThe crude solid was dissolved in THF (5 mL)
13. customThe volatiles were removed in vacuo
14. customThe residue was dried under hi-vacuum
15. dissolutiondissolved in MeOH/DCM
16. additionfollowed by addition of silica gel
17. concentrationThe contents were concentrated to dryness
18. customdried under hi-vacuum for 1 h
19. customThe contents were purified by silica gel chromatography (dry loaded, eluent: 3-95% gradient chloroform (containing 10% 2M ammonia in methanol) and DCM)
20. customThe collected solid was triturated from hot acetonitrile
21. filtrationThe contents were filtered cold
22. washwashed with additional acetonitrile
23. customThe title compound was collected as 90 mg (41%)