Methanol → propane-2-sulfonic acid {2,4-difluoro-3-[methoxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenyl}-amide

HRID 1098377Notes

Reaction equation

HRID 1098377 reaction equation
[F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13].[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]2[CH:25]=[C:26]3[CH:32]=[CH:31][NH:30][C:27]3=[N:28][CH:29]=2)[CH:19]=1.[OH-].[K+].O.[CH3:36]O>>[F:1][C:2]1[C:7]([CH:8]([O:9][CH3:36])[C:32]2[C:26]3[C:27](=[N:28][CH:29]=[C:24]([C:20]4[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=4)[CH:25]=3)[NH:30][CH:31]=2)=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 14797Potassium HydroxideHCID 513585515-(Pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridineHCID 58086031N-(2,4-difluoro-3-formylphenyl)propane-2-sulfonamide

Product 1

HCID 58087136propane-2-sulfonic acid {2,4-difluoro-3-[methoxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenyl}-amide

Procedure

To propane-2-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (60, 220.0 mg, 0.83 mmol) in methanol (15 mL) was added 5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine (89, 150.0 mg, 0.77 mmol, prepared as described in Example 17) and potassium hydroxide (537.0 mg, 9.6 mmol) under an atmosphere of nitrogen. The reaction was stirred at room temperature overnight. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtrated. The filtrate was concentrated and purified by silica gel column chromatography eluting with 5% methanol in dichloromethane to give the compound (61, 160 mg, 45.3%). In this step, minor compound Propane-2-sulfonic acid {2,4-difluoro-3-[methoxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenyl}-amide was also formed and isolated. MS (ESI) [M+H+]+=460.1.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 5% methanol in dichloromethane
  8. customto give the compound (61, 160 mg, 45.3%)

Sources & evidence

ORD record
ord-51636cb266574079b1d437c92c0f3a18
Source dataset
uspto-grants-2012_03
Patent number
US08143271B2

Reaction notes

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