合成路线1

1) By refluxing N-cyano-N',S-dimethylisoithiourea (B) and 5-methyl-4-[(2-aminoethyl)thiomethyl imidazol (III) in acetonitrile. The latter is prepared by reacting cysteamine (A) and 5-methyl-4-(hydroxymethyl)imidazol (II) (from 5-methylimidazol (I) and formalin) in acetic acid, in hydrochloric acid or in hydrobromic acid. 2) By reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with cyanodithioimido carbonic (C) acid dimethyl ester to give the isothiourea (IV), followed by reaction with methylamine. 3) By refluxing 1-methyl-3-[2-[[(5-methylimidazol-4-yl)-methyl]thio]ethyl]-2-thiourea (metiamide) (V) and lead cyanamide. The first is prepared by reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with methyl isocyanate (D).

合成路线2

The synthesis of CP-93,318 is summarized: Treatment of 4-methyl-5-imidazolemethanol (I) with thionyl chloride affords chloromethylimidazole (II). Exposure of (II) to potassium cyanide provides nitrile (III), and subsequent reaction of (III) with diethyldithiophosphate in the presence of hydrochloric acid gives thioamide (IV), as its hydrochloride salt. Condensation of this hygroscopic salt with 2-bromo-2'-methoxyacetophenone (V) provides thiazole CP-93,318. Analogues of CP-93,318, modified at the methoxyphenyl moiety, were prepared similarly by condensation of convergent intermediate (IV) and the appropriate alpha-haloketone.

合成路线3

1) Treatment of 4-methyl-5-hydroxymethylimidazole (I) with trimethylsilyl chloride and triethylamine followed by reaction with N,N-dimethylsulfamoyl chloride gives the protected imidazole (II). Removal of the trimethylsilyl group by means of tetrabutylammonium fluoride affords the 5-hydroxymethylimidazole (III), which is converted into the chloromethylimidazole (IV) with thionyl chloride.

合成路线4

合成路线5