Acetoxyacetyl chloride → 3-(1-cyano-1-methylethyl)-N-(5-{[2-(glycoloylamino)-1,3-benzothiazol-6-yl]oxy}-2-methylphenyl)benzamide

HRID 2190385Notes

Reaction equation

HRID 2190385 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[CH:14][C:15]([CH3:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.C([O:36][CH2:37][C:38](Cl)=[O:39])(=O)C>N1C=CC=CC=1>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:16]1[CH:17]=[C:12]([O:11][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:37](=[O:36])[CH2:38][OH:39])[S:3][C:4]=3[CH:10]=2)[CH:13]=[CH:14][C:15]=1[CH3:32])=[O:31])([CH3:27])[CH3:28])#[N:30]

Participants

4

Reactant 2

HCID 26297Acetoxyacetyl chlorideHCID 86646002N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 866553613-(1-cyano-1-methylethyl)-N-(5-{[2-(glycoloylamino)-1,3-benzothiazol-6-yl]oxy}-2-methylphenyl)benzamideYield 53%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of N-{5-[(2-amino-1,3-benzothiazol-6-yl)oxy]-2-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.452 mmol) produced in Example A7(vi) in pyridine (4.0 mL) was added 2-chloro-2-oxoethyl acetate (107 μL, 0.994 mmol), and the mixture was stirred at room temperature for 10 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methanol (4.0 mL). 1N Aqueous sodium hydroxide solution (4.0 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was neutralized with 1N hydrochloric acid, and extracted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL) and saturated brine (50 mL), successively, 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 basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether to give the title compound (120 mg, 53%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in methanol (4.0 mL)
  3. addition1N Aqueous sodium hydroxide solution (4.0 mL) was added
  4. stirringthe mixture was stirred at room temperature for 1 hr
  5. extractionextracted with ethyl acetate (100 mL)
  6. washThe organic layer was washed with water (50 mL) and saturated brine (50 mL)
  7. dry with materialsuccessively, and dried over anhydrous sodium sulfate
  8. filtrationThe insoluble material was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→80/20)
  11. concentrationthe obtained solution was concentrated under reduced pressure
  12. customThe residue was triturated with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-20c68157ed8145b6891a8b283bd3b7ce
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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