4-Toluenesulfonyl chloride → N-[4-({3-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3,5-difluorophenyl]acetamide

HRID 2192150Notes

Reaction equation

[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[O:11][C:12]2[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[CH:14][C:13]=2[F:23])[NH:4][CH:3]=1.C([Li])CCC.[C:29]1([CH3:39])[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>C1COCC1>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[O:11][C:12]2[C:17]([F:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[CH:14][C:13]=2[F:23])[N:4]([S:35]([C:32]2[CH:33]=[CH:34][C:29]([CH3:39])=[CH:30][CH:31]=2)(=[O:37])=[O:36])[CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

1.37 g (3.58 mmol) of N-{4-[(3-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluorophenyl}acetamide are dissolved in 200 ml of THF and cooled to −78° C. 1.6 ml (4.0 mmol) of a 2.5M n-butyllithium solution are added dropwise, and the mixture is stirred for 15 min. 752 mg (3.94 mmol) of p-toluenesulfonyl chloride as a solution in 7.5 ml of THF are then added dropwise. The reaction solution is allowed to warm to RT and stirred for one hour. The mixture is then partitioned between ethyl acetate and 0.1N aqueous sodium hydroxide solution. The aqueous phase is extracted twice with ethyl acetate. The combined organic phases are dried over magnesium sulfate and the solvent is removed under reduced pressure. The product is purified by column chromatography on silica gel (mobile phase: dichloromethane/acetone 20:1 to 10:1).

Workup

temperatureto warm to RT
stirringstirred for one hour
customThe mixture is then partitioned between ethyl acetate and 0.1N aqueous sodium hydroxide solution
extractionThe aqueous phase is extracted twice with ethyl acetate
dry with materialThe combined organic phases are dried over magnesium sulfate
customthe solvent is removed under reduced pressure
customThe product is purified by column chromatography on silica gel (mobile phase: dichloromethane/acetone 20:1 to 10:1)

Sources & evidence

ORD record: ord-caf2a0b0e8364f32a6ca99ba40c66cfe
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329716B2

Reaction notes

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