Cesium carbonate → 4-[2-(2,4-difluorophenoxy)-5-(methylsulfonyl)phenyl]-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 930888노트

반응식

HRID 930888 반응식
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]1[C:13]2[CH:22]=[CH:21][N:20](S(C3C=CC(C)=CC=3)(=O)=O)[C:14]=2[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1.[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[OH:41].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[F:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[O:41][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]1[C:13]2[CH:22]=[CH:21][NH:20][C:14]=2[C:15](=[O:19])[N:16]([CH3:18])[CH:17]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 1230512,4-DifluorophenolHCID 89657423HCID 89657423, 화합물

생성물 1

HCID 896561064-[2-(2,4-difluorophenoxy)-5-(methylsulfonyl)phenyl]-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one수율 80%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

A mixture of Example 138a (0.05 g, 0.105 mmol), 2,4-difluorophenol (0.016 g, 0.126 mmol), and cesium carbonate (0.069 g, 0.211 mmol) in DMSO (1 mL) was heated at 120° C. for 16 hours. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate three times. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by reverse phase Preparative HPLC (10-80% acetonitrile in 0.1% TFA/water) to give the title compound (0.036 g, 0.084 mmol, 79% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 12.10 (s, 1H), 7.99 (d, J=2.44 Hz, 1H), 7.86 (dd, J=8.54, 2.44 Hz, 1H), 7.40-7.56 (m, 3H), 7.31 (t, J=2.9 Hz, 1H), 7.14-7.20 (m, 1H), 6.98 (d, J=8.54 Hz, 1H), 6.28-6.30 (m, 1H), 3.59 (s, 3H), 3.26 (s, 3H). MS (ESI+) m/z 431.1 (M+H)+.

후처리

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. extractionThe aqueous layer was extracted with additional ethyl acetate three times
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase Preparative HPLC (10-80% acetonitrile in 0.1% TFA/water)

출처 및 근거

ORD 기록
ord-fa0d29f04be24a99a0576be85cfe6c79
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296741B2

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