Bromine → Methyl 2-amino-6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylate

HRID 455232Notes

Reaction equation

HRID 455232 reaction equation
[S-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:35]#[N:36])([CH3:34])[CH3:33])[CH:27]=3)=[O:25])[CH:18]=2)=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12].BrBr>C(O)(=O)C>[NH2:3][C:2]1[S:1][C:15]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:35]#[N:36])([CH3:33])[CH3:34])[CH:27]=4)=[O:25])[CH:18]=3)[CH:8]=[CH:7][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 24408BromineHCID 516872Potassium thiocyanateHCID 66810422Methyl 5-amino-2-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]benzoate

Product 1

HCID 71818881Methyl 2-amino-6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylateYield 90.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

Potassium thiocyanate (1.02 g, 10.5 mmol) was suspended in acetic acid (10 mL), and the mixture was stirred at room temperature for 10 min. A solution of methyl 5-amino-2-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]benzoate (1.13 g, 2.62 mmol) in acetic acid (10 mL) was added to the obtained solution, and the mixture was further stirred at room temperature for 10 min. A solution of bromine (460 mg, 2.88 mmol) in acetic acid (5 ml) was slowly added dropwise to the obtained solution, and the mixture was stirred at room temperature for 3 hr. The resulting yellow insoluble material was filtered off and washed with acetic acid. The filtrate and washings were combined and the mixture was concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (200 mL), washed successively with saturated aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL×2), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was is concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0), and the obtained solution was concentrated under reduced pressure to give the title compound (1.15 g, 90%) as a white powder.

Workup

  1. stirringthe mixture was further stirred at room temperature for 10 min
  2. stirringthe mixture was stirred at room temperature for 3 hr
  3. filtrationThe resulting yellow insoluble material was filtered off
  4. washwashed with acetic acid
  5. concentrationthe mixture was concentrated under reduced pressure
  6. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationInsoluble material was filtered off
  9. concentrationthe filtrate was is concentrated under reduced pressure
  10. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0)
  11. concentrationthe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-57f783da73e144e09cc07751aff43a95
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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