Chloroacetyl chloride → 5-Amino-3-(3,5-dimethylphenyl)-2-(4-pyridyl)-7H-thiazolo[3,2-a]pyrimidin-7-one

HRID 1370277Notes

Reaction equation

HRID 1370277 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]([NH2:20])[S:12][C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[CH2:22][C:23](Cl)=[O:24].[CH3:26][N:27](C)C(=O)C>>[NH2:27][C:26]1[N:10]2[C:9]([C:4]3[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=3)=[C:13]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[S:12][C:11]2=[N:20][C:23](=[O:24])[CH:22]=1

Participants

4

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 31374DimethylacetamideHCID 9925734[4-(3,5-Dimethylphenyl)-5-(4-pyridyl)-1,3-thiazol-2-yl)amine

Product 1

HCID 185109905-Amino-3-(3,5-dimethylphenyl)-2-(4-pyridyl)-7H-thiazolo[3,2-a]pyrimidin-7-oneYield 18%

Conditions

Temperature
80 °C

Procedure

To a solution of [4-(3,5-dimethylphenyl)-5-(4-pyridyl)-1,3-thiazol-2-yl)amine (1.0 g) in N,N-dimethylacetamide (10 mL) was added chloroacetyl chloride (0.60 g) and the mixture was stirred at 80° C. for 14 hours. N,N-Dimethylacetamide was distilled off under reduced pressure and the resultant residue was dissolved in dimethylsulfoxide (5 mL). To this solution was added sodium cyanate (0.24 g) and the mixture was stirred at room temperature for 14 hours. An aqueous solution of sodium hydrogen carbonate was added to the reaction mixture and the mixture was extracted with a mixed solvent of ethyl acetate-tetrahydrofuran (1:1). The extract was washed with brine, dried over anhydrous sodium sulfate and filtered. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane-tetrahydrofuran, 1:1) and recrystallized from ethanol to obtain the title compound (0.22 g, yield 18%).

Workup

  1. distillationN,N-Dimethylacetamide was distilled off under reduced pressure
  2. dissolutionthe resultant residue was dissolved in dimethylsulfoxide (5 mL)
  3. additionTo this solution was added sodium cyanate (0.24 g)
  4. stirringthe mixture was stirred at room temperature for 14 hours
  5. additionAn aqueous solution of sodium hydrogen carbonate was added to the reaction mixture
  6. extractionthe mixture was extracted with a mixed solvent of ethyl acetate-tetrahydrofuran (1:1)
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe solvent was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (hexane-tetrahydrofuran, 1:1)
  12. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-313d727434e949a983cda567823399e5
Source dataset
uspto-grants-2003_06
Patent number
US06583146B1

Reaction notes

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