Hydrochloric Acid → 6-(2-chloroethyl)-7-methyl-5H-(1,3)thiazolo(3,2-a)pyrimidin-5-one

HRID 1381863Notes

Reaction equation

HRID 1381863 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].[C:7]([CH:10]1[CH2:14][CH2:13][O:12][C:11]1=O)(=O)[CH3:8].Cl.P(Cl)(Cl)([Cl:19])=O>O.CC1C=CC=CC=1>[Cl:19][CH2:13][CH2:14][C:10]1[C:11](=[O:12])[N:3]2[CH:4]=[CH:5][S:1][C:2]2=[N:6][C:7]=1[CH3:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 21552-AminothiazoleHCID 106012-AcetylbutyrolactoneHCID 24813Phosphorus oxychloride

Product 1

HCID 8178726-(2-chloroethyl)-7-methyl-5H-(1,3)thiazolo(3,2-a)pyrimidin-5-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 50 parts of 2-thiazolamine, 76 parts of 3-acetyl-4,5-dihydro-2(3H)-furanone, 1.2 parts of concentrate hydrochloric acid and 270 parts of methylbenzene was stirred and refluxed for 2 hours using a water-separator. The reaction mixture was cooled and 340 parts of phosphoryl chloride were added at a temperature between 20° and 30° C. The whole was heated slowly to 100°-110° C. and stirring was continued for 2 hours at this temperature. The reaction mixture was evaporated and the residue was poured into a mixture of crushed ice and ammonium hydroxide. 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-propanol and 1,1'-oxybisethane, yielding 36 parts of 6-(2-chloroethyl)- 7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (intermediate 5).

Workup

  1. temperaturerefluxed for 2 hours
  2. temperatureThe reaction mixture was cooled
  3. temperatureThe whole was heated slowly to 100°-110° C.
  4. stirringstirring
  5. customThe reaction mixture was evaporated
  6. additionthe residue was poured into a mixture of crushed ice and ammonium hydroxide
  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-propanol and 1,1'-oxybisethane

Sources & evidence

ORD record
ord-e56e4617b56245b9acc75d38628da1cb
Source dataset
uspto-grants-1989_02
Patent number
US04804663

Reaction notes

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