Potassium Carbonate → 3-(1-cyano-1-methylethyl)-N-(4-ethyl-3-{[2-(glycoloylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}phenyl)benzamide

HRID 1800474Notes

Reaction equation

HRID 1800474 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[CH:13]=[C:14]([NH:20][C:21](=[O:33])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=3)[CH:15]=[CH:16][C:17]=1[CH2:18][CH3:19])[N:5]=2.C([O:37][CH2:38][C:39](Cl)=[O:40])(=O)C.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1>[C:31]([C:28]([C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[C:21]([NH:20][C:14]1[CH:15]=[CH:16][C:17]([CH2:18][CH3:19])=[C:12]([O:11][C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:38](=[O:37])[CH2:39][OH:40])=[N:10][C:9]3=[CH:8][CH:7]=2)[CH:13]=1)=[O:33])([CH3:30])[CH3:29])#[N:32]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 26297Acetoxyacetyl chlorideHCID 86646003N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 595070603-(1-cyano-1-methylethyl)-N-(4-ethyl-3-{[2-(glycoloylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}phenyl)benzamideYield 44%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-ethylphenyl}-3-(1-cyano-1-methylethyl)benzamide (150 mg, 0.327 mmol) in pyridine (4.0 mL) was added 2-chloro-2-oxoethyl acetate (56 μL, 0.523 mmol), and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, the obtained residue was dissolved in methanol (10 mL), potassium carbonate (45 mg, 0.327 mmol) was added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, neutralized with 1% aqueous citric acid solution, and extracted with ethyl acetate (100 mL). The organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), 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→85/15), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether/hexane to give the title compound (73.6 mg, 44%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in methanol (10 mL)
  3. stirringthe mixture was stirred at room temperature for 4 hr
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. extractionextracted with ethyl acetate (100 mL)
  6. washThe organic layer was washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  7. dry with materialdried 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→85/15)
  11. concentrationthe obtained solution was concentrated under reduced pressure
  12. customThe residue was triturated with ethyl acetate/diisopropyl ether/hexane

Sources & evidence

ORD record
ord-c9f3bbfa872f46289bbb876739893607
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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