Hydrogen Bromide → 6-(N-(4-bromo-3-(difluoromethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 2272315Notes

Reaction equation

N([O-])=O.[Na+].N[C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[CH:40]([F:42])[F:41].[BrH:43]>C(#N)C.CCOC(C)=O.O.[Cu]Br>[Br:43][C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[CH:40]([F:42])[F:41]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium nitrite (0.12 g, 1.75 mmol) was added to a 0° C. solution of 6-(N-(4-amino-3-(difluoromethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.87 g, 1.59 mmol) in acetonitrile (10 ml) and aq HBr (48%) (10 mL). The reaction mixture was stirred for 30 min at 0° C. and copper (I) bromide (0.27 g, 1.91 mmol) was added. The reaction mixture was stirred at 75° C. for 2 h and diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-50% EtOAc/hexanes) to afford the title compound (0.38 g, 39%) as a white foam. LCMS (m/z, ES+)=607, 609 (M+H+).

Workup

stirringThe reaction mixture was stirred at 75° C. for 2 h
washThe organic layer was washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated
custompurified by silica gel chromatography (0-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-3090ae4e3ac6450a84ab26c98c21df9f
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09119868B2

Reaction notes

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