Methanol → 3-[2,6-difluoro-3-(propane-1-sulfonylamino)-phenyl]-hydroxy-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester

HRID 250605Notes

Reaction equation

HRID 250605 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1)=[O:4].[F:14][C:15]1[C:20](C=O)=[C:19]([F:23])[CH:18]=[CH:17][C:16]=1[NH:24][S:25]([CH2:28][CH2:29][CH3:30])(=[O:27])=[O:26].[OH-:31].[K+].O.[CH3:34]O>>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:13]([C:20]3[C:19]([F:23])=[CH:18][CH:17]=[C:16]([NH:24][S:25]([CH2:28][CH2:29][CH3:30])(=[O:26])=[O:27])[C:15]=3[F:14])=[C:12]([OH:31])[N:11]([CH3:34])[C:8]2=[N:9][CH:10]=1)=[O:4]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 14797Potassium HydroxideHCID 22832049methyl 1H-pyrrolo[2,3-b]pyridine-5-carboxylateHCID 53419003N-(2,4-Difluoro-3-formylphenyl)-1-propanesulfonamide

Product 1

HCID 666463523-[2,6-difluoro-3-(propane-1-sulfonylamino)-phenyl]-hydroxy-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl esterYield 28%

Procedure

To 1H-Pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester (532, 155.0 mg, 0.88 mmol) in methanol (15.0 mL) were added propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (73, 260.0 mg, 0.99 mmol, prepared as described in Example 7) and potassium hydroxide (859 mg, 15.3 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 dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% ethyl acetate in hexane to give the compound as white solid (P-1545, 110 mg, 28%). MS (ESI) [M+H+]+=440.2.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified by silica gel column chromatography
  6. washeluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-3f00e72315e845d2a10c6cc372121c0a
Source dataset
uspto-grants-2011_01
Patent number
US07863288B2

Reaction notes

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