Studies on Pyrazolo [3, 4-d] pyrimidine Derivatives. IV. On 1-Methyl-and 1-Phenyl-1H-pyrazolo [3, 4-d] pyrimidine 5-Oxide

Various reactions usually carried out on heterocyclic N-oxides were examined on 1-methyl-(IIm-0) and 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine 5-oxide (IIp-0) prepared from the condensation-cyclization of 1-methyl-(IIIm-1) or 1-phenyl-5-amino-4-hydroxyiminomethyl-1H-pyrazole (IIIp-1) and ethyl orthoformate. The reaction of IIp-0 with alkaline solution gave the ring fission product between the 5- and 6-position such as 5-formamido- (IIIp-5) and 5-amino-4-hydroxyiminomethyl-1-phenyl-1H-pyrazole (IIIp-1). Application of the Reissert reaction to II-0 resulted in the formation of the ring fission products such as O-benzoyl derivative of IIIp-1 (IIIp-6) and 5-amino-1-methyl-1H-pyrazole-4-carbonitrile (IIIm-3). Acetic anhydride and IIm-0 gave 1-methyl-1H-pyrazolo [3, 4-d] pyrimidin-4-ol-(Im-4). But the reaction with IIp-0 gave both 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-4-ol (Ip-4) and 5-acetamido-1-phenyl-1H-pyrazole-4-carbonitrile (IIIp-8). Ip-4 was also obtained from the reaction of IIp-0 with tosyl chloride. The thermal decomposition of II-0 afforded 4, 4'-bis [1-methyl-1H-pyrazolo [3, 4-d] pyrimidine] (IXm) and 4, 4'-bis [1-phenyl-1H-pyrazolo [3, 4-d] pyrinidime] (IXp) together with 1-methyl-(Im-0) and 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine (Ip-0). The Grignard reaction of II-0 gave 1-Methyl-(IIm-7-9) and 1-phenyl-4-alkyl-1H-pyrazolo-[3, 4-d] pyrimidine 5-oxide (IIp-5-9). Im-0 and II-0 were transformed into 1-methyl-(XIXm) and 1-phenyl-1H-pyrazolo [3, 4-b] pyridines (XIXp) by the reaction with some active methylene compounds or ketone such as malononitrile (A-1), ethyl cyanoacetate (A-2), ethyl acetoacetate (A-3), acetylacetone (A-4) and cyclohexanone (A-5). Thus, in the presence of ethoxide ion Im-0 reacted with A-1 to give 6-amino-1-methyl-1H-pyrazolo [3, 4-d] pyridine-5-carbonitrile (XIXm-1). The direct reaction of IIm-0 with A-1 and A-2 gave 4, 5-dihydro-5-hydroxy-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-malononitrile (XXm) and ethyl α-cyano-4, 5-dihydro-5-hydroxy-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-acetate (XXm-2). But the direct reaction with A-3, 4 and 5 afforded the corresponding XIXm (XIXm-3, 4, and 5), respectively. The reaction of IIp-0 with A-1, 3, and 4 formed the corresponding XIXp (XIXp-1, 3, and 4) together with IXp (in the case of A-3 and 4), Ip-0 (in the case of A-4) and the ring fission product such as ethyl 2-(4-cyano-1-phenyl-1H-pyrazol-5-ylaminomethylene)-3-oxobutyrate (XXIp-3) and ethyl 2-(4-hydroxy-iminomethyl-1-phenyl-1H-