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

HRID 930888Notes

Reaction equation

HRID 930888 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-fa0d29f04be24a99a0576be85cfe6c79
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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