Hydrogen Bromide → HCID 131732296, compound

HRID 1424843Notes

Reaction equation

HRID 1424843 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27]([NH:29][CH3:30])=[O:28])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[S:36]([CH3:39])(=[O:38])=[O:37].[BrH:40].N([O-])=O.[Na+].S(=O)(O)[O-].[Na+]>C(#N)C.O.[Cu]Br.CCOC(C)=O.CCCCCC.CCOC(C)=O>[Br:40][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27]([NH:29][CH3:30])=[O:28])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[S:36]([CH3:39])(=[O:38])=[O:37]

Participants

10

Reactant 4

HCID 260Hydrogen BromideHCID 23665763Sodium BisulfiteHCID 23668193Sodium NitriteHCID 131732294HCID 131732294, compound

Product 1

HCID 131732296HCID 131732296, compoundYield 68%

Reagents, catalysts & solvents 5

HCID 24593copper(I) bromideCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-(N-(4-amino-3-(methylsulfonyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.4 g, 0.700 mmol) in acetonitrile (3 mL) was added 8M HBr (0.437 mL, 3.50 mmol). The resulting solution was cooled in an ice water bath for 15 minutes and the mixture was treated with a solution of sodium nitrite (0.072 g, 1.050 mmol) in water (2 mL) over 5 min. The resulting yellow suspension was stirred in an ice bath for 1.5 hours and then treated with copper(I) bromide (0.201 g, 1.399 mmol) in small portions over 5 minutes. This dark brown solution that was warmed to 60° C. and stirring continued for additional 2 h. The mixture was cooled to RT and poured into a mixture of 5% aqueous sodium bisulfite (6 mL) and EtOAc (80 mL). The phases were separated and the aqueous solution extracted with two additional 15 mL portions of EtOAc. The combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated aqueous sodium bicarbonate, saturated brine, dried over sodium sulfate and concentrated to dryness at reduced pressure to give a yellow foam. This material was subjected to flash chromatography (silica gel, gradient from 9:1 hexane/EtOAc to EtOAc) to afford the title compound (0.3 g, 68%). LCMS (m/z, ES+)=635, 637 (M+H+).

Workup

  1. temperatureThe resulting solution was cooled in an ice water bath for 15 minutes
  2. stirringstirring
  3. waitcontinued for additional 2 h
  4. temperatureThe mixture was cooled to RT
  5. customThe phases were separated
  6. extractionthe aqueous solution extracted with two additional 15 mL portions of EtOAc
  7. washThe combined EtOAc solutions were washed with 5% aqueous sodium bisulfite, saturated aqueous sodium bicarbonate, saturated brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness at reduced pressure
  10. customto give a yellow foam

Sources & evidence

ORD record
ord-af04cd4e598940698d00718520267013
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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