反应详情

温度

60 °C

An oven-dried vial was charged with 3-amino-2,3-dimethylbutan-2-ol (0.063 g, 0.539 mmol), 2-chloro-4-fluoro-3-((trimethylsilyl)ethynyl)benzonitrile (Example 32B) (0.113 g, 0.449 mmol), and K2CO3 (0.137 g, 0.988 mmol) and sealed with a rubber septum. Anhyd NMP (3 mL) was added via syringe and the mixture was stirred in a heating block at 60° C. under N2. After 1 h, the vial was sealed with a PTFE-faced crimp top and subjected to microwave heating; 1 h at 140° C. followed by 45 min at 160° C. (with air cooling). The mixture was poured into water/EtOAc and the whole was filtered through a pad of Celite. Layers of the filtrate were separated and the aqueous layer was extracted with EtOAc (×2). Combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (C18 stationary phase, MeCN/water gradient with 0.1% TFA additive) affording 4-chloro-1-(3-hydroxy-2,3-dimethylbutan-2-yl)-1H-indole-5-carbonitrile (0.0066 g, 5% yield) as a tan solid (ca. 85% purity): 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J=9.0 Hz, 1H), 7.49 (d, J=3.5 Hz, 1H), 7.32 (d, J=8.9 Hz, 1H), 6.71 (d, J=3.4 Hz, 1H), 1.87 (s, 6H), 1.20 (s, 6H); MS (LCMS ES+) m/z 277 ([M+H]+, 65%), 318 ({[M+H]+MeCN}+, 100%).

1. customsealed with a rubber septum
2. temperatureto microwave heating
3. wait1 h at 140° C. followed by 45 min at 160° C.
4. temperature(with air cooling)
5. filtrationthe whole was filtered through a pad of Celite
6. customLayers of the filtrate were separated
7. extractionthe aqueous layer was extracted with EtOAc (×2)
8. washCombined organics were washed (water, brine)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in vacuo
11. customThe residue was purified by preparative HPLC (C18 stationary phase, MeCN/water gradient with 0.1% TFA additive)