1,1-Dichloroacetone → HCID 178479418, Verbindung

Beteiligte Stoffe

Reaktionsschritte

Famotidine is a well-known histamine H2-receptor antagonist and gastric acid secretion inhibitor. A key intermediate for the preparation of this compound is N-[4-(cyanoethylthiomethyl)-2-thiazolyl]guanidine (also known as N-[4-[[(2-cyanoethyl)-thio]methyl]-2-thiazoyl]guanidine). To prepare this intermediate U.S. Pat. Nos. 4,562,261 and 4,609,737 describe a route based on N-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride as the starting material. The synthesis involves preparing this starting material by portionwise addition of (aminoiminomethyl)thiourea to dichloroacetone in acetone at temperatures of about -5° to -7° C. and stirring the resultant mixture for 5 days at below 0° C. The resultant N-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride is isolated, purified and converted to N-[4-[[(2-aminoiminomethyl)thio]methyl]-2-thiazoyl]guanidine) dihydrochloride by reaction with thiourea. Without isolating this intermediate, the reaction mixture is cooled below 10° C. and to the solution are added 3-chloropropionitrile and isopropyl alcohol, followed by dropwise addition of aqueous NaOH whereby crystals of N-[4-(cyanoethylthiomethyl)-2-thiazolyl]guanidine are formed.

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