Toluene → 1-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-

HRID 60085

Reaction equation

HRID 60085 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C1(C)C=CC=CC=1.C(N(C(C)C)CC)(C)C.[Cl:44][C:45]1[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:46]=1[C:47](Cl)=[O:48]>CN(C)C1C=CN=CC=1.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][N:8]([C:47](=[O:48])[C:46]3[C:45]([Cl:44])=[CH:53][CH:52]=[CH:51][C:50]=3[Cl:54])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 119845561-Propanesulfonamide, N-[3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl]-

Product 1

HCID 510010251-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-Yield 36%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Into a reaction flask under nitrogen, propane-1-sulfonic acid [3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide (9, 8.40 g, 18.3 mmol) is combined with 100 mL of toluene, 4-dimethylaminopyridine (447 mg, 3.7 mmol), diisopropylethylamine (4.74 g, 36.7 mmol) and 2,6-dichloro-benzoyl chloride (10, 4.34 g, 20.7 mmol). The reaction is stirred at room temperature overnight, then diluted with 300 mL of dichloromethane and washed with 200 mL of saturated aqueous sodium bicarbonate, then 200 mL of brine. The organic layer is 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 to provide crude material that is further purified with additional chromatography, eluting with 1:1 hexane:dichloromethane up to 100% dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (11, 4.15 g, 36%).

Workup

  1. washwashed with 200 mL of saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer is dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material is purified by silica gel column chromatography
  6. washeluting with a gradient of ethyl acetate
  7. customto provide crude material that
  8. customis further purified with additional chromatography
  9. washeluting with 1:1 hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-fe0a24062281490d88f21fda7438aaba
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Linked notes

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