Potassium Hydroxide → propane-1-sulfonic acid 2,4-difluoro-3-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-phenyl-amide

HRID 1639580Notes

Reaction equation

HRID 1639580 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[NH:7][CH:8]=[CH:9][C:2]=12.[F:10][C:11]1[C:16]([CH:17]=[O:18])=[C:15]([F:19])[CH:14]=[CH:13][C:12]=1[NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22].[OH-].[K+].[Cl-].[NH4+]>O.CO>[F:10][C:11]1[C:16]([CH:17]([OH:18])[C:9]2[C:2]3[C:3](=[N:4][CH:5]=[CH:6][N:1]=3)[NH:7][CH:8]=2)=[C:15]([F:19])[CH:14]=[CH:13][C:12]=1[NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 53708035H-Pyrrolo[2,3-b]pyrazineHCID 53419003N-(2,4-Difluoro-3-formylphenyl)-1-propanesulfonamide

Product 1

HCID 58001696propane-1-sulfonic acid 2,4-difluoro-3-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-phenyl-amideYield 50.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To 5H-pyrrolo[2,3-b]pyrazine (3, 0.150 g, 1.26 mmol) and propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (8, 0.388 g, 1.47 mmol), 2.2 mL of methanol was added. This suspension was allowed to stir for 10 minutes, followed by the addition of potassium hydroxide (0.230 g, 4.10 mmol). The reaction was allowed to stir at room temperature for 7 hours, then poured into 5 mL of water and 5 mL of saturated ammonium chloride and extracted with 5 mL of ethyl acetate. The organic layer was separated and concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography eluting with a gradient of 10 to 100% ethyl acetate in hexanes. Appropriate fractions were combined and concentrated under vacuum to give the desired compound (9, 243 mg). MS (ESI)[(M-18)+H+]+=365.1.

Workup

  1. stirringto stir at room temperature for 7 hours
  2. extractionextracted with 5 mL of ethyl acetate
  3. customThe organic layer was separated
  4. concentrationconcentrated under vacuum
  5. customthe resulting residue was purified by silica gel column chromatography
  6. washeluting with a gradient of 10 to 100% ethyl acetate in hexanes
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b1a3fde2acea411e837f310435778345
Source dataset
uspto-grants-2012_02
Patent number
US08110576B2

Reaction notes

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