反应详情

温度

150 °C

In a microwave tube were charged with of N—((S)-1-(3-bromo-6-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide (45 mg, 0.07 mmol), N-(1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide (36 mg, 0.1 mmol) and PdCl2[P(Cy)3]2 (5 mg, 0.007 mmol). To the mixture was added 1.4 mL of 1,4-dioxane and 0.2 mL of sodium bicarbonate aqueous solution (1M). The system was purged with argon and then the microwave tube was sealed and the reaction mixture was heated up in a microwave synthesizer at 150° C. for 20 min. After cooled down to room temperature, it was partitioned between EtOAc and water. The organic layer was separated and washed with brine, then dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC eluting with acetonitrile and water (with 0.1% TFA) to afford the title product. 1H NMR (400 MHz, methanol-d4) δ 7.79 (dd, 1H), 7.51 (dd, 1H), 7.29-6.45 (m, 5H), 6.48-6.24 (m, 2H), 4.85 (m, 3H), 4.19-3.91 (m, 4H), 3.58-2.75 (m, 8H), 2.49 (m, 2H), 1.61 (d, J=2.2 Hz, 3H), 1.41 (q, J=7.0 Hz, 1H), 1.20-0.83 (m, 1H). MS (m/z) 789.11 [M+H]+.

1. customThe system was purged with argon
2. customthe microwave tube was sealed
3. temperatureAfter cooled down to room temperature
4. customit was partitioned between EtOAc and water
5. customThe organic layer was separated
6. washwashed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by reverse phase HPLC
11. washeluting with acetonitrile and water (with 0.1% TFA)