Hydrochloric Acid → 5-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione

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Reaction Steps

19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F254; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.

Provenance & Evidence