Acetic Anhydride → propane-1-sulfonic acid{3-[5-(1-acetyl-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

HRID 60088Notes

Reaction equation

HRID 60088 reaction equation
[F:1][C:2]1[C:7]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[CH:20]=[C:21]5[C:25](=[CH:26][CH:27]=4)[NH:24][N:23]=[CH:22]5)[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[C:6]([F:28])[CH:5]=[CH:4][C:3]=1[NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31].[C:36](OC(=O)C)(=[O:38])[CH3:37]>C(#N)C>[C:36]([N:24]1[C:25]2[C:21](=[CH:20][C:19]([C:16]3[CH:17]=[C:18]4[C:10]([C:8]([C:7]5[C:2]([F:1])=[C:3]([NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:31])=[O:32])[CH:4]=[CH:5][C:6]=5[F:28])=[O:9])=[CH:11][NH:12][C:13]4=[N:14][CH:15]=3)=[CH:27][CH:26]=2)[CH:22]=[N:23]1)(=[O:38])[CH3:37]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 53261781propane-1-sulfonic acid(2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbony]-phenyl)-amide

Product 1

HCID 53261842propane-1-sulfonic acid{3-[5-(1-acetyl-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a round bottom flask, propane-1-sulfonic acid {2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide (P-0001, 0.020 g, 0.040 mmol) is combined with acetic anhydride (0.023 mL, 0.24 mmol) and 4 mL of acetonitrile. The reaction is stirred at room temperature for 3 hours, then concentrated under vacuum, combined with water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of 20-100% ethyl acetate (with 2% acetic acid) in hexanes. Appropriate fractions are combined and concentrated under vacuum, and the resulting solid is further washed with a mixture of ethyl acetate:hexanes to provide the desired compound. MS (ESI) [M+H+]+=538.0.

Workup

  1. concentrationconcentrated under vacuum
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe resulting material is purified by silica gel column chromatography
  7. washeluting with a gradient of 20-100% ethyl acetate (with 2% acetic acid) in hexanes
  8. concentrationconcentrated under vacuum
  9. washthe resulting solid is further washed with a mixture of ethyl acetate

Sources & evidence

ORD record
ord-b9fbfcf1d6cf4f5f8a5283b30c3613be
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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