GB812366A — Improvements in and relating to derivatives of pyrimidine and the preparation thereof

USPTO Abstract

The invention comprises pyrrolo (2,3-d) pyrimidines of the general formula (I) (wherein X is a hydrogen atom or a hydroxy, amino or mercapto group and Y is a hydrogen or chlorine atom or a hydroxy, amino or mercapto group). These are prepared by cyclising acetals of the general formula (II) by the action of a strong acid, such as sulphuric acid, in a solvent such as 95 peer cent ethanol, followed if desired by interconversion of X and Y by processes of chlorination, amination, thiation or dethiation. <FORM:0812366/IV (b)/1> <FORM:0812366/IV (b)/2> In examples, 2,4-dihydroxy-, 2-mercapto-4-hydroxy -, 2 - mercapto - 4 - amino -, 2 - amino-4 - hydroxy -, 2,4 - diamino -, 4 - hydroxy - and 2 - hydroxy - 4 - amino - pyrrolo (2,3 - d)-pyrimidine are prepared from the corresponding acetals; pyrrolo (2,3-d) pyrimidine and 4-hydroxypyrrolo (2,3-d) pyrimidine are prepared by dethiating 4 - mercapto - and 2 - mercapto - 4-hydroxy-pyrrolo (2,3-d) pyrimidine respectively; 4 - chloropyrrolo (2,3-d) pyrimidine is prepared by the action of phosphorus oxychloride on the corresponding hydroxy compound, and converted to 4-mercaptopyrrolo (2,3-d)-pyrimidine by the action of thiourea, and to 4-aminopyrrolo (2,3-d) pyrimidine by the action of ammonia. Also described is an alternative preparation of 2,4-dihydroxypyrrolo (2,3-3) pyrimidine by heating together 6-amino-2,4-dihydroxypyrimidine and chloroacetaldehyde in aqueous sodium acetate. 2,4 - Dihydroxy - 6 - amino - 5 - diethoxyethylpyrimidine is prepared from urea and ethylacetalcyanoacetate (itself prepared from ethyl cyanoacetate and bromoacetal), 2-mercapto-4-hydroxy - 6 - amino - 5 - diethoxyethylpyrimidine from thiourea and ethylacetalcyanoacetate, 2-mercapto - 4,6 - diamino - 5 - diethoxyethylpyrimidine from thiourea and acetalmalononitrile, 2,6 - diamino - 4 - hydroxy - 5 - diethoxyethylpyrimidine from guanidine and ethylacetalcyanoacetate, 2,4,6 - triamino - 5 - diethoxyethylpyrimidine from guanidine and acetalmalonitrile and 2 - hydroxy - 4,6 - diamino - 5 - diethoxyethylpyrimidine from urea and acetalmalonitrile.