反应详情

Method Q Add N-[1-isopropyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indol-6-yl]-methanesulfonamide (50.0 mg, 0.132 mmoles), 4-bromo-3-methyl-benzonitrile (51.8 mg, 0.264 mmoles), Pd(OAc)2 (4.25 mg, 0.018 mmoles; 4.25 mg), 2-(diphenylphosphino)-2′-(N,N-dimethylamino)biphenyl (11.5 mg, 0.030 mmoles), potassium phosphate (84.2 mg, 0.396 mmoles), and 1,4-dioxane (1.00 mL) to a 10 mL microwave vessel, equipped with a stir bar. Purge the reaction mixture with nitrogen, and then seal the vessel with a cap. Place the vessel in a microwave reactor at 150° C. for 15 min at 250 W heating. Monitor the reaction using LC/MS. Cool the reaction to ambient temperature and quench with saturated aqueous ammonium chloride. Extract the resulting mixture into ethyl acetate. Wash the combined extracts with saturated aqueous ammonium chloride, water and brine. Dry the resulting solution over sodium sulfate (granular) and concentrate in vacuo. Dissolve the resulting solid in dichloromethane and purify on a chromatotron (1MM silica gel plate) 0-2% ethyl acetate gradient in dichloromethane. A second purification may be necessary. This time purify the material with 30-40% ethyl acetate gradient in hexane to provide N-[3-(4-Cyano-2-methyl-phenyl)-1-isopropyl-1H-indol-6-yl]-methanesulfonamide, 35 mg (75%) as an off white solid. 1H NMR (CDCl3) δ 7.58 (s, 1H), 7.45-7.52 (m, 3), 7.41 (d, 1H, J=8.4 Hz), 7.25 (s, 1H), 6.9 (dd, 1H, J=8.4, 1.7 Hz), 6.52 (s, 1H), 4.65 (septet, 1H, J=6.7 Hz), 2.98 (s, 3H), 2.34 (s, 3H), 1.55 (d, 6H, J=6.7 Hz); MS (IS−) m/e 377 (M−1).

1. customequipped with a stir bar
2. customPurge the reaction mixture with nitrogen
3. customseal the vessel with a cap
4. customat 150° C.
5. customfor 15 min
6. temperatureheating
7. temperatureCool
8. customthe reaction to ambient temperature
9. customquench with saturated aqueous ammonium chloride
10. extractionExtract the resulting mixture into ethyl acetate
11. washWash the combined extracts with saturated aqueous ammonium chloride, water and brine
12. dry with materialDry the resulting solution over sodium sulfate (granular)
13. concentrationconcentrate in vacuo
14. dissolutionDissolve the resulting solid in dichloromethane
15. custompurify on a chromatotron (1MM silica gel plate) 0-2% ethyl acetate gradient in dichloromethane
16. customA second purification
17. customThis time purify the material with 30-40% ethyl acetate gradient in hexane