Hydrochloric Acid → 6-(2-Chloroethyl)-3,7-dimethyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

HRID 325912Notes

Reaction equation

HRID 325912 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH2:7])[S:5][CH:6]=1.[C:8]([CH:11]1[CH2:15][CH2:14][O:13][C:12]1=O)(=O)[CH3:9].Cl.P(Cl)(Cl)([Cl:20])=O>CC1C=CC=CC=1>[Cl:20][CH2:14][CH2:15][C:11]1[C:12](=[O:13])[N:3]2[C:2]([CH3:1])=[CH:6][S:5][C:4]2=[N:7][C:8]=1[CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 106012-AcetylbutyrolactoneHCID 24813Phosphorus oxychlorideHCID 741432-Amino-4-methylthiazole

Product 1

HCID 134778116-(2-Chloroethyl)-3,7-dimethyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 40 parts of 4-methyl-2-thiazolamine, 30 parts of 3-acetyl-4,5-dihydro-2(3H) furanone and 225 parts of methylbenzene was stirred and refluxed for 2.50 hours with 0.6 parts of hydrochloric acid. After cooling to room temperature, 170 parts of phosphoryl chloride were added. The whole was heated slowly to about 110° C. and stirring was continued for 2 hours at this temperature. The reaction mixture was evaporated and the residue was poured onto crushed ice. Ammonium hydroxide was added till a pH of 8 was reached. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanol, yielding 19.3 parts of 6-(2-chloroethyl)-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin- 5-one (intermediate 1).

Workup

  1. temperatureThe whole was heated slowly to about 110° C.
  2. stirringstirring
  3. customThe reaction mixture was evaporated
  4. additionthe residue was poured
  5. customonto crushed ice
  6. additionAmmonium hydroxide was added till a pH of 8
  7. extractionThe product was extracted with trichloromethane
  8. customThe extract was dried
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column-chromatography over silica gel using
  12. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  13. customThe pure fractions were collected
  14. customthe eluent was evaporated
  15. customThe residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanol

Sources & evidence

ORD record
ord-1d385b0f5bd941ba882109e0acf0d88a
Source dataset
uspto-grants-1984_04
Patent number
US04443451

Reaction notes

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