Hydrogen Bromide → HCID 131732259, compound

HRID 1424797Notes

Reaction equation

HRID 1424797 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]([Cl: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[Cl:36].[BrH:37].N([O-])=O.[Na+]>C(#N)C.O>[Br:37][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]([Cl: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[Cl:36]

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 23668193Sodium Nitrite2×HCID 131732258HCID 131732258, compound

Product 1

HCID 131732259HCID 131732259, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of 6-(N-(4-amino-3-chlorophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5-cyclopropyl-N-methylbenzofuran-3-carboxamide (0.421 g, 0.773 mmol) in 25 mL of acetonitrile was treated with 25 mL of 48% aqueous HBr and the resulting suspension cooled in an ice water bath. To the mixture was added a solution of sodium nitrite (0.056 g, 0.812 mmol) in 2 mL of water. After stirring at 0° C. for 30 minutes an additional 14 mg portion of sodium nitrite in 1 mL of water was added. After stirring at 0° C. for another 30 minutes, the mixture was treated with CuBr (0.130 g, 0.906 mmol) in four portions over 5 minutes. The mixture was warmed to 60° C. for 30 minutes and then cooled to RT. The mixture was partitioned between EtOAc and 5% aqueous sodium bisulfite. The EtOAc solution was washed with 5% aqueous sodium bisulfite (2×), saturated aqueous sodium bicarbonate (2×), brine (1×), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient from hexane to 3:7 hexane/EtOAc) followed by recrystallization from hexane/EtOAc to give the title compound (0.212 g, 45%) as a white solid. LCMS (m/z, ES+)=609 (M+H+).

Workup

  1. temperaturethe resulting suspension cooled in an ice water bath
  2. additionwas added
  3. temperatureThe mixture was warmed to 60° C. for 30 minutes
  4. temperaturecooled to RT
  5. customThe mixture was partitioned between EtOAc and 5% aqueous sodium bisulfite
  6. washThe EtOAc solution was washed with 5% aqueous sodium bisulfite (2×), saturated aqueous sodium bicarbonate (2×), brine (1×)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to dryness at reduced pressure
  9. customThe crude product was purified by flash chromatography (silica gel, gradient from hexane to 3:7 hexane/EtOAc)
  10. customfollowed by recrystallization from hexane/EtOAc

Sources & evidence

ORD record
ord-1d3e1508039248378ef2e71fbcbdcf81
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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