Patent ID: 6559317
Filing Date: 2003-05-06
Classification: A61P,C07D

Abstract:
A process for preparing 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazole-5-thiono-1-yl)-propan-2-ol of the Formula (I) comprising the steps of:a) in a first step, reacting 2-(1-chloro-cycloprop-1-yl)-2-(2â€²-chloro-benzyl)-oxirane of the Formula (II) â€ƒwith hydrazine hydrate in the presence of aromatic hydrocarbon, optionally in the presence of acetonitrile to form a mixture, and introducing into said mixture hydrogen chloride or extracting said mixture with aqueous hydrochloric acid to form 2-(1-chloro-cycloprop-1-yl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazine hydrochloride of the Formula (III) b) in a second step, treating the resulting 2-(1-chloro-cycloprop-1-yl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazine hydrochloride of the Formula (III) â€ƒwith alkali metal hydroxide in the presence of water and in the presence of aromatic hydrocarbon, optionally in a mixture with a lower alcohol, or in the presence of alkyl alkylcarboxylate, and then reacting successively with formaldehyde and thiocyanate of the Formula (IV) Xâ€”SCNâ€ƒâ€ƒ(IV), â€ƒwherein X represents sodium, potassium or ammonium, â€ƒin the presence of water and in the presence of aromatic hydrocarbon, optionally in a mixture with a lower alcohol, or in the presence of alkyl alkylcarboxylate and, optionally, in the presence of a catalyst to form 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane of the Formula (V) andc) in a third step, reacting the resulting 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane of the Formula (V) â€ƒwith iron(III) chloride in the presence of aqueous hydrochloric acid and in the presence of an inert organic diluent.