Bromine → HCID 57387326, compound

HRID 1800570Notes

Reaction equation

HRID 1800570 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 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 (50 mL) was added dropwise bromine (2.40 g, 15 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. The yellow insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. To the residue was added saturated aqueous sodium hydrogen carbonate solution (200 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0), and triturated with diethyl ether to give the title compound (3.32 g, 69%) as a pale-yellow amorphous.

Workup

  1. temperaturecooling
  2. filtrationThe yellow insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionTo the residue was added saturated aqueous sodium hydrogen carbonate solution (200 mL)
  5. extractionthe mixture was extracted with ethyl acetate (100 mL×2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0)
  10. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-5107dee713c74a0ab05a2f93dff32941
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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