Pyrazolo-pyrimidines, halogenation

A halogen substituent at C-4 of the pyrazolo[3,4-c ]pyrimidine ring system is readily replaced by active methylene reagents (76S824, 76YZ1352). For example, treatment of the derivatives (207) with active methylene reagents in the presence of sodium hydride results in the formation of derivatives (208) in 70-80% yield (Equation (21)). The methylsulfonyl derivative (209) is converted into the carboxamide (211) when treated with cyanide ion intermediacy of the nitrile (210) seems most likely (Scheme 16) <82JMC1334>. 

Scheme 87 illustrates two potentially useful routes to the pyrazolo[3,4-rf]pyrimidine system. In (290) the usual higher reactivity of the halogen at C(4) is seen (see Section 4.05.3.3). Ethylamine monosubstitutes at room temperature, but disubstitution requires a temperature of 100 °C (75S645). Cyanoguanidine converts the aminopyrazole (263) into the pyrazolotriazine (291) on heating at 160 C (57G597). 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

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