反应详情

A vial was charged with N-(2,4-dimethoxybenzyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide (Intermediate J) (77.2 mg, 0.118 mmol) and DMF (1 mL) to give a clear solution. Sodium hydride (60% in mineral oil) (7.06 mg, 0.177 mmol) was added in one portion to give a bright yellow mixture. The mixture was stirred for 45 min, then iodomethane (14.72 μl, 0.235 mmol) was added. After stirring for an additional 1 h, the mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in DCM (0.9 mL) and TFA (0.18 mL), and the resulting mixture was stirred for 1.5 h. The mixture was diluted with MeOH (5 mL), then filtered through Celite® (diatomaceous earth) with the aid of methanol. The filtrate was concentrated, and the crude product was purified by chromatography on silica gel (0 to 10% MeOH/DCM) to afford 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-6-sulfonamide (51.42 mg, 0.099 mmol, 84% yield) as a white foam. 1H NMR (400 MHz, DMSO-d6) δ=8.48 (s, 1 H), 7.97-7.85 (m, 3 H), 7.83-7.78 (m, 1 H), 7.61 (d, J=8.3 Hz, 1 H), 7.53 (s, 1 H), 7.38 (d, J=1.9 Hz, 1 H), 6.35 (d, J=1.9 Hz, 1 H), 3.75 (s, 3 H), 3.28 (s, 3 H). m/z (ESI) 520.1 (M+H)+.

1. customto give a clear solution
2. customto give a bright yellow mixture
3. stirringAfter stirring for an additional 1 h
4. extractionextracted with EtOAc (2×)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. stirringTFA (0.18 mL), and the resulting mixture was stirred for 1.5 h
9. additionThe mixture was diluted with MeOH (5 mL)
10. filtrationfiltered through Celite® (diatomaceous earth) with the aid of methanol
11. concentrationThe filtrate was concentrated
12. customthe crude product was purified by chromatography on silica gel (0 to 10% MeOH/DCM)