Cesium carbonate → 5-bromo-3-(2-(2,4-difluorophenoxy)-5-nitrophenyl)-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridine

HRID 633597Notes

Reaction equation

HRID 633597 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12]([C:13]3[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=3F)=[CH:11][N:10]([CH3:23])[C:5]2=[C:6]([O:8][CH3:9])[N:7]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[OH:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:12]([C:13]3[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=3[O:32][C:26]3[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:25]=3[F:24])=[CH:11][N:10]([CH3:23])[C:5]2=[C:6]([O:8][CH3:9])[N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1230512,4-DifluorophenolHCID 904176845-bromo-3-(2-fluoro-5-nitrophenyl)-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridine

Product 1

HCID 904161975-bromo-3-(2-(2,4-difluorophenoxy)-5-nitrophenyl)-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridineYield 77%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of Example 182A (367 mg, 0.965 mmol), 2,4-difluorophenol (111 μl, 1.158 mmol) and cesium carbonate (472 mg, 1.448 mmol) in 8 mL DMSO was heated under nitrogen at 90° C. for 1.5 hours. The mixture was partitioned between water and ethyl acetate (80 mL). The aqueous phase was extracted with ethyl acetate (2×60 mL). The combined organics were washed with water (2×), saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel with a gradient of 10-70% ethyl acetate in heptanes to give the title compound (331 mg, 0.742 mmol, 77% yield) as a yellow solid.

Workup

  1. customThe mixture was partitioned between water and ethyl acetate (80 mL)
  2. extractionThe aqueous phase was extracted with ethyl acetate (2×60 mL)
  3. washThe combined organics were washed with water (2×), saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by column chromatography on silica gel with a gradient of 10-70% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-afd6f75300f544318d5325cf04d77f86
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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