Hydrochloric Acid → 6-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

HRID 1032294Notes

Reaction equation

HRID 1032294 reaction equation
[CH3:1][C:2]1[S:6][C:5]([NH2:7])=[N:4][N:3]=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>O.CC1C=CC=CC=1>[Cl:20][CH2:14][CH2:15][C:11]1[C:12](=[O:13])[N:4]2[N:3]=[C:2]([CH3:1])[S:6][C:5]2=[N:7][C:8]=1[CH3:9]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 106012-AcetylbutyrolactoneHCID 24813Phosphorus oxychlorideHCID 669491,3,4-Thiadiazole, 2-amino-5-methyl-

Product 1

HCID 155864606-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 58 parts of 5-methyl-1,3,4-thiadiazol-2-amine, 76 parts of 3-acetyl-4,5-dihydro-2(3H)-furanone, 1.2 parts of hydrochloric acid solution 12N and 540 parts of methylbenzene was stirred and refluxed for 2 hours using a water-separator. After cooling to room temperature, there were added dropwise 340 parts of phosphoryl chloride at 20°-40° C. (cooling was necessary to keep that temperature). The whole was gradually heated to reflux: at 95° C. Hydrogen chloride gas evolution was started. Then 100 parts of the mixture were distilled off and the residue was stirred and refluxed for 2 hours. After cooling, the reaction mixture was evaporated and the residue was poured into an ice/ammonium hydroxide mixture while stirring. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified three times by column-chromatography over silica gel using each time 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 2,2'-oxybispropane, yielding 11.8 parts of 6-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one; mp. 118° C. (int. 14).

Workup

  1. temperaturerefluxed for 2 hours
  2. temperaturecooling
  3. temperatureThe whole was gradually heated
  4. temperatureto reflux
  5. customat 95° C
  6. distillationThen 100 parts of the mixture were distilled off
  7. stirringthe residue was stirred
  8. temperaturerefluxed for 2 hours
  9. temperatureAfter cooling
  10. customthe reaction mixture was evaporated
  11. additionthe residue was poured into an ice/ammonium hydroxide mixture
  12. stirringwhile stirring
  13. extractionThe product was extracted with trichloromethane
  14. customThe extract was dried
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue was purified three times by column-chromatography over silica gel using each time
  18. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  19. customThe pure fractions were collected
  20. customthe eluent was evaporated
  21. customThe residue was crystallized from 2,2'-oxybispropane

Sources & evidence

ORD record
ord-a640e93c8aff4e358360c6d43f1594a3
Source dataset
uspto-grants-1990_09
Patent number
US04957916

Reaction notes

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