Hydrogen Bromide → HCID 131732316, compound

HRID 1424867Notes

Reaction equation

HRID 1424867 reaction equation
N[C:2]1[C:11]([F:12])=[CH:10][C:9]([N:13]([C:18]2[C:37]([CH:38]3[CH2:40][CH2:39]3)=[CH:36][C:21]3[C:22]([C:32](=[O:35])[NH:33][CH3:34])=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[O:24][C:20]=3[CH:19]=2)[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].S(=O)(=O)(O)[O-].[Na+].C([O-])(O)=O.[Na+].[BrH:56]>C(#N)C.O.CCOC(C)=O.[Cu]Br>[Br:56][C:2]1[C:11]([F:12])=[CH:10][C:9]([N:13]([C:18]2[C:37]([CH:38]3[CH2:40][CH2:39]3)=[CH:36][C:21]3[C:22]([C:32](=[O:35])[NH:33][CH3:34])=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[O:24][C:20]=3[CH:19]=2)[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 516919Sodium BisulfateHCID 23668193Sodium NitriteHCID 131732315HCID 131732315, compound

Product 1

HCID 131732316HCID 131732316, compoundYield 64%

Reagents, catalysts & solvents 4

HCID 24593copper(I) bromideCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of methyl 2-amino-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-3-fluorobenzoate (601 mg, 1.055 mmol) in acetonitrile (6 mL) and conc. HBr (6 mL, 48% aq) was cooled in an ice-water bath and then treated with a solution of sodium nitrite (95 mg, 1.372 mmol) in water (1 mL). After 15 min, copper(I) bromide (182 mg, 1.266 mmol) was added to the mixture. The mixture was then heated to 50° C. After 30 min, the solution was cooled to room temperature and diluted with EtOAc. Sodium bisulfate (15 mL, 5% aq) and saturated aqueous NaHCO3 solution (20 mL) were added to the solution. The organic phase was separated and washed by brine (40 mL), dried over Na2SO4, concentrated and then purified by silica gel chromatography(0-35% EtOAc in hexanes) to give methyl 2-bromo-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-3-fluorobenzoate (430 mg, 64% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.55 (br. s., 1H), 0.75-0.93 (m, 2H), 0.97 (d, J=6.6 Hz, 1H), 1.88-2.04 (m, 1H), 3.01 (d, J=4.9 Hz, 3H), 3.28 (s, 3H), 3.91 (s, 3H), 5.72-5.85 (m, 1H), 7.21 (t, J=8.6 Hz, 2H), 7.33 (dd, J=10.0, 2.8 Hz, 1H), 7.49 (dd, J=2.8, 1.3 Hz, 1H), 7.52 (s, 1H), 7.58 (s, 1H), 7.85-7.92 (m, 2H). LCMS (m/z, ES+)=633, 635 (M+H+).

Workup

  1. waitAfter 30 min
  2. temperaturethe solution was cooled to room temperature
  3. customThe organic phase was separated
  4. washwashed by brine (40 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography(0-35% EtOAc in hexanes)

Sources & evidence

ORD record
ord-42d5d1ada398409a9d1f7585c28ea633
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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