Bromine → N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamide

HRID 2190405Notes

Reaction equation

HRID 2190405 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:15][C:16](=[O:28])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]4([C:26]#[N:27])[CH2:25][CH2:24]4)[CH:18]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])=[CH:4][CH:3]=1.[S-:31][C:32]#[N:33].[K+].BrBr>C(O)(=O)C>[NH2:33][C:32]1[S:31][C:3]2[CH:4]=[C:5]([O:6][C:7]3[CH:8]=[C:9]([NH:15][C:16](=[O:28])[C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]5([C:26]#[N:27])[CH2:25][CH2:24]5)[CH:18]=4)[CH:10]=[CH:11][C:12]=3[O:13][CH3:14])[CH:29]=[CH:30][C:2]=2[N:1]=1

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 67311871N-[3-(4-aminophenoxy)-4-methoxyphenyl]-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 86655365N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]-4-methoxyphenyl}-3-(1-cyanocyclopropyl)benzamideYield 54.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution (10 mL) of N-[3-(4-aminophenoxy)-4-methoxyphenyl]-3-(1-cyanocyclopropyl)benzamide (1.74 g, 4.36 mmol) in acetic acid was added potassium thiocyanate (1.46 g, 15.0 mmol), and the mixture was stirred at room temperature for 30 min. To the obtained transparent solution was added dropwise bromine (1.20 g, 7.50 mmol) under ice-cooling, and the reaction mixture was stirred at room temperature for 18 hr. The precipitated yellow powder was filtered off through celite, and the filtrate was concentrated under reduced pressure. To the residue was added 0.1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane/ethyl acetate=1:1), and triturated with diethyl ether to give the title compound (1.08 g, 54%) as a yellow solid.

Workup

  1. temperaturecooling
  2. stirringthe reaction mixture was stirred at room temperature for 18 hr
  3. filtrationThe precipitated yellow powder was filtered off through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionTo the residue was added 0.1N aqueous sodium hydroxide solution
  6. extractionthe mixture was extracted with ethyl acetate
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent:hexane/ethyl acetate=1:1)
  10. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-ca427912bacc470c84cf818062a7c47e
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

Loading…