Verfahren zur Herstellung von Purinderivaten

摘要

Purine or substituted purines are prepared by successive reduction of a 4-amino-5-arylazopyrimidine of one of the formulae and and imidazole ring formation in a single reaction stage at atmospheric pressure and without isolation of intermediate product. Each of X1 and Y1 represents H, NH2, OH, SH, hydrazino, C1- 4 alkyl, mono- or di(C1- 4 alkyl)amino acylamino, C1- 4 alkylmercapto, C1- 4 alkoxy, C1- 4 alkylhydrazino, arylhydrazino, or semicarbazido, only one of X1 and Y1 being OH at any one time, each of X2 and Y2 represents NH, O, S, NOH, arylhydrazono, C1- 4 alkylhydrazono or semicarbazono, R1 represents hydrogen, C1- 4 alkyl, hydroxyl, C1- 4 alkoxy, halogen, nitro, sulpho or carboxyl, n is 0, 1, 2 or 3, and each of R2 and R3 is C1- 3 alkyl. The reduction i effected in the presence of a reducing agent and the imidazole ring formation is effected in the presence of at least one of the following, viz. formamide, formamidine, formic acid, a C1- 4 alkyl formate, ammonium formate, a di(C1- 4 alkoxy) methyl C1- 4 alkanoate, a (C1- 4 alkyl) formimino-ether, a C1- 4 alkyl orthoformate, a combination of a C1- 4 alkyl orthoformate and acetic anhydride, a combination of a C1- 4 alkyl orthoformate and ammonia, a combination of a C1- 4 alkyl orthoformate and a ketene, a combination of a C1- 4 alkyl orthoformate and a nitrile, and a combination of a C1- 4 alkyl orthoformate, ammonia and a salt of a C1- 4 organic acid. The reduction and imidazole ring formation may be carried out in one and the same solvent, and the latter may also function as the cyclizing agent. The preparation is described of guanine, adenine (as sulphate and free base), xanthine, purine, 2 - hydroxy - purine, isoguanine, 3-methyl - guanine, hypoxanthine, 3 - methylxanthine, 2 - amino - purine, 2,6 - diaminopurine, 2 - methylmercapto - 6 - amino - purine, 2 - methyl - 6 - dimethyl - purine and 2 methyl-hypoxanthine.