Pyridine → 1-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-

HRID 60084

Reaction equation

HRID 60084 reaction equation
[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([Br:20])[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.ClCCl.N1C=CC=CC=1.[CH2:31]([S:34](Cl)(=[O:36])=[O:35])[CH2:32][CH3:33]>O>[Br:20][C:17]1[CH:18]=[C:19]2[C:11]([C:9]([C:4]3[C:3]([F:21])=[C:2]([NH:1][S:34]([CH2:31][CH2:32][CH3:33])(=[O:36])=[O:35])[CH:7]=[CH:6][C:5]=3[F:8])=[O:10])=[CH:12][NH:13][C:14]2=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 6344DichloromethaneHCID 662791-Propanesulfonyl chloride2×HCID 58368727(3-Amino-2,6-difluorophenyl)(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)methanone

Product 1

HCID 119845561-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-Yield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Into a reaction flask under nitrogen, (3-amino-2,6-difluoro-phenyl)-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (7, 13.00 g, 36.9 mmol) is combined with 150 mL of dichloromethane and anhydrous pyridine (5.84 g, 73.8 mmol), and propane-1-sulfonyl chloride (8, 6.05 g, 42.5 mmol) is added. The reaction is stirred at room temperature overnight, and additional pyridine (1.46 g, 18.5 mmol) and propane-1-sulfonyl chloride (1.51 g, 10.6 mmol) are added. The reaction is stirred at room temperature another 3 hours, then diluted with 500 mL of water and extracted 3×250 mL with dichloromethane. The organic layers are combined and washed with 250 mL of brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of ethyl acetate:hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (9, 8.41 g, 50%).

Workup

  1. additionis added
  2. stirringThe reaction is stirred at room temperature another 3 hours
  3. extractionextracted 3×250 mL with dichloromethane
  4. washwashed with 250 mL of brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material is purified by silica gel column chromatography
  9. washeluting with a gradient of ethyl acetate
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4caf914248cd4248a5cff86edd2d7c76
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Linked notes

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