Pyrazolo 3,4-rf pyrimidines

The 4-hydrazino-pyrazolo[3,4-rf]pyrimidine derivative 80 yields pyrazolo[4,3-e]-[l,2,4]triazolo[4,3-c]pyrimidinones 82 through hydrazone derivatives 81 <00JCS(P1)33>, these compounds being a new class of potential xanthine oxidase inhibitors. 

Several pyrazolo[3,4-rf pyrimidine derivatives were prepared via reaction of 289 with reagents that can furnish an N-C fragment, for example, urea, thiourea, and formamide <2002BML1687>. 

Many spectral data have not been unequivocally assigned. Data that were assigned correctly have been summarized (84MI2). H-NMR shifts of pyrazolo[l,5-a]pyrimidine are shown in 294. C-NMR data of pyrazolo-[3,4-rf]pyrimidine-6-one and of pyrazolo[3,4-d]pyrimidin-7-one are shown in 295 and 296 (73JHC431). C-NMR data of some other pyrazolo[3,4-d]-pyrimidines have been reported (73JHC43I 84MI2). 

For nonfunctionally substituted fully conjugated azoloazines, only pyrazoloazines and imid-azoazines exhibit this type of tautomerism. Four tautomeric forms are possible for pyrazolo[3,4-rf]-pyrimidine (18, 80-82) (Scheme 1). In the solid state as well as in neutral media, this compound exists as structure (18). In basic media the anion (83a, b) is the predominant species (Equation (2)). In acidic solutions the cation (84a,b) predominates (Equation (3)) <58JCS2973>. 

Benzylidenehydrazinouracils (514), derived from 6-hydrazinouracils (513) and aldehydes, are cyclized upon UV irradiation and treatment with thionyl chloride or NBS, to afford pyrazolo[3,4-rf]pyrimidines (516), depending on the presence of protons at R2 and/or R3 (Scheme 51) fully methylated hydrazones are decomposed into 6-methylaminouracils (515) and nitriles <73S300, 74H(2)153, 75BCJ1484, 84JHC969, 92AHC(55)129>. 

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). 

Oxidative cyclization of the fully methylated 6-(benzylidenehydrazino)uracils (536) provides a 90% yield of the pyrazolo[3,4-rf]pyrimidines (537) (75BCJ1484). 

The formamide reaction has been successfully used to convert a 2-amino-pyridine-3-carboxamide to pyrido[2,3-d]pyrimidin-4-ones (see 3)220 3-aminopyrazole-4-carboxamide (see 15) to pyrazolo[3,4-rf ] pyrimidin-4-ones (see 16)118 4-aminopyrazole-3-carboxamide to pyrazolo[4,3-d]pyrimi-din-7-ones (see 17)221 many 4-amino-1,2,3-triazole-5-carboxamides (see 20) to 8-azapurin-6-ones (see 21)157,217-222—226 and 4-aminoimidazole-5-car-boxamides (see 18) to purin-6-ones (see 19).124-202-227 228 Secondary amines are suitable starting materials, as in the conversion of 4-amino-l,2,3-triazole-5-(jV-methyl)carboxamide and its 3-benzyl63 and... 

I. PYRAZOLO[3,4-rf]PYRIMIDINE C-NUCLEOSIDES 1. Pyrazolo[3,4-d]pyrimidin-6-yl C-Nucleosides... 

Anhydronucleosides of pyrazolo[3,4-rf]pyrimidines have been prepared by 2, 3 -rra/i5-elimination of the corresponding xylofuranosyl systems. When the a-hydroxyphosphonate 16 (see Vol. 29, p. 291 and earlier) was desilylated and then treated with triflyl chloride, the epoxyphosphonate 17 was obtained, and a 2, 3 -epoxy-2 -phosphonate was made similarly. ... 

Pyrazolecarboxamides react with carbon disulfide in boiling pyridine with a loss of hydrogen sulfide molecule to give 6-thioxo-4,5,6,7-tetrahydro-4H-pyrazolo[3,4-rf] pyrimidine-4-ones (70%-86% yields, Scheme 2.108, Table 2.12) [578]. 

---