Dimethylformamide → 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

HRID 1524418노트

반응식

HRID 1524418 반응식
COC1C=C(OC)C=CC=1C[N:6]([C:35]1[S:39][N:38]=[CH:37][N:36]=1)[S:7]([C:10]1[N:15]=[C:14]2[NH:16][CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=3[C:29]3[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=3)[C:13]2=[CH:12][CH:11]=1)(=[O:9])=[O:8].[CH3:46]N(C=O)C.[H-].[Na+].IC>O>[CH3:46][N:16]1[C:14]2=[N:15][C:10]([S:7]([NH:6][C:35]3[S:39][N:38]=[CH:37][N:36]=3)(=[O:8])=[O:9])=[CH:11][CH:12]=[C:13]2[C:18]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][C:20]=2[C:29]2[N:33]([CH3:34])[N:32]=[CH:31][CH:30]=2)=[CH:17]1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 71259592N-(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-sulfonamide2회

생성물 1

HCID 712594731-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-sulfonamide수율 84%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-069229dc821d44bb81ed3af2dd7609f9
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079902B2

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