Bromine → HCID 57387326, compound

HRID 1800659Notes

Reaction equation

HRID 1800659 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([F:30])=[C:13]([NH:15][C:16](=[O:29])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]4([C:26]#[N:27])[CH2:25][CH2:24]4)[C:18]=3[Cl:28])[CH:14]=2)=[N:6][CH:7]=1.[S-:31][C:32]#[N:33].[K+].BrBr>C(O)(=O)C>[NH2:33][C:32]1[S:31][C:7]2[C:2]([N:1]=1)=[CH:3][CH:4]=[C:5]([O:8][C:9]1[CH:10]=[CH:11][C:12]([F:30])=[C:13]([NH:15][C:16](=[O:29])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]4([C:26]#[N:27])[CH2:24][CH2:25]4)[C:18]=3[Cl:28])[CH:14]=1)[N:6]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 57387083HCID 57387083, compound

Product 1

HCID 57387326HCID 57387326, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution (50 mL) of N-{5-[(5-aminopyridin-2-yl)oxy]-2-fluorophenyl}-2-chloro-3-(1-cyanocyclopropyl)benzamide (4.23 g, 10 mmol) and potassium thiocyanate (3.89 g, 40 mmol) in acetic acid was added dropwise bromine (2.40 g, 15 mmol) at 15° C., and the mixture was stirred at room temperature for 6 hr. The yellow suspension was filtered through celite, and the yellow insoluble material was thoroughly washed with acetic acid (50 mL). The filtrate and washing solution were combined, and the mixture was concentrated under reduced pressure. The residue was suspended in 0.1N aqueous sodium hydroxide solution (100 mL), and the suspension was extracted with ethyl acetate (100 mL). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=100/0→0/100). The obtained residue was crystallized from diethyl ether to give the title compound (3.32 g, 69%) as a pale-yellow powder.

Workup

  1. filtrationThe yellow suspension was filtered through celite
  2. washthe yellow insoluble material was thoroughly washed with acetic acid (50 mL)
  3. washThe filtrate and washing solution
  4. concentrationthe mixture was concentrated under reduced pressure
  5. extractionthe suspension was extracted with ethyl acetate (100 mL)
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=100/0→0/100)
  9. customThe obtained residue was crystallized from diethyl ether

Sources & evidence

ORD record
ord-f2b03be7e7cf467bad50af9e016b7d3f
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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