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

HRID 217617Notes

Reaction equation

HRID 217617 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[F:11][C:12]1[C:17]([CH:18]=[O:19])=[C:16]([F:20])[CH:15]=[CH:14][C:13]=1[NH:21][S:22]([CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:24])=[O:23].[OH-].[K+].[Cl-].[Na+]>C(OCC)(=O)C.CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:18]([OH:19])[C:17]3[C:12]([F:11])=[C:13]([NH:21][S:22]([CH2:25][CH:26]([CH3:27])[CH3:28])(=[O:24])=[O:23])[CH:14]=[CH:15][C:16]=3[F:20])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 14797Potassium HydroxideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 583169302-Methyl-propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide

Product 1

HCID 595695972-methyl-propane-1-sulfonic acid {3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-2,4-difluoro-phenyl}-amideYield 89.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a reaction vial, 5-bromo-1H-pyrrolo[2,3-b]pyridine (55, 287 mg, 1.46 mmol), 2-methyl-propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (59, 445 mg, 1.60 mmol) and potassium hydroxide (246 mg, 4.38 mmol) are combined with 7 mL of methanol and stirred at room temperature overnight. The reaction was combined with ethyl acetate and aqueous saturated sodium chloride, and extracted. The organic layer was washed with water, brine, and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was treated with 75 mL of acetonitrile:water 4:1 with 5% trifluoroacetic acid and stirred overnight at room temperature. The reaction was combined with ethyl acetate and aqueous saturated sodium chloride, and extracted. The organic layer was washed with water, brine, and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound (68, 618 mg).

Workup

  1. extractionextracted
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. additionThe residue was treated with 75 mL of acetonitrile:water 4:1 with 5% trifluoroacetic acid
  7. stirringstirred overnight at room temperature
  8. extractionextracted
  9. washThe organic layer was washed with water, brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-5babb612c47e4960859885557c47db43
Source dataset
uspto-grants-2012_06
Patent number
US08198273B2

Reaction notes

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