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

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Reaction Steps

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).

Provenance & Evidence