Journal Article

Syntheses of pyrazolo [3,4-d]pyrimidines with an amino group in 3- or 4-position are described. For the preparation of the 3-amino derivatives a 4-chloro-5-cyano-pyrimidine is condensed with various hydrazines. The 4-amino-pyrazolo [3,4-d]pyrimidines are obtained by reacting 3-amino-4-carbethoxy-pyrazoles with formamide, chlorinating thc 4-hydroxy-pyrazolo [3,4-d]pyrimidines, and substituting the halogen by amino groups. Some of the compounds show diuretic and cardiac activity, others inhibit tumor-growth.

The preparation of the paraxanthine, theobromine and theophylline isomers 1,5-; 2,5- and 1,7-; 2,7- and 5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro-pyrazolo[3,4-d]-pyrimidines is described and their structure established. A structurally specific synthesis of the caffeine and isocaffeine isomers 1,5,7- and 2,5,7-trimethyl-4,6- dioxo-4,5,6,7-tetrahydro-pyrazolo [3,4-d]pyrimidines has been realized.

The preparation of the caffeine isomers 1,5,7- and 2,5,7-trimethyl-4, 6-dioxo-4,5,6,7-tetrahydro-pyrazolo[3,4-d]pyrimidines is described and their structures established. The compounds exhibit diuretic and cardiac activity.

Various monosubstituted hydrazines have been reacted with ethoxymethylenemalononitrile to yield the corresponding l-substituted-5-amino-4-cyanopyrazolcs (IV). Treatment of IV with concentrated sulfuric acid gave the corresponding l-substituted-5-aminopyr~zole-4carbosmides (XVI). The structure of 5-amino-1-phenylpyrazole-4-carbosamidewas established by an unambiguous synthesis. The preparation of 1-alkyl- and l-argl-l-aminoayrazolo[3,4-d]pyriniidineshas been accomplished by treating the corre- sponding 1-alkyl(or aryl)-5-amino-4-cyanopyrazole (IV) with boiling formamide.

Conrad and Zart' treated ethyl cyanoacetate with phenylhydrazine, using sodium alcoholate as a condensing agent, and obtained a colorless compound of the composition C9H9N30and the m. p. 219". This, they assumed to be l-phenyl-3- hydroxy-5-pyrazolone-imide,I. However, the reaction between ethyl cyanoacetate and phenyl- hydrazine could also lead to the isomeric l-phenyl- 3-amino-5-pyrazolone, 11.

In the first paper of this series it was shown that the compound synthesized by Conrad and Zart and called 1-phenyl-3-hydroxy-5-pyrazoloinmeide is in fact the isomeric l-phenyl-3-amino-5-pyrazlone I. The real l-phenyl-3-hydroxy-5-pyrazolone imide I1 has now been prepared. Phenylhydrazine was condensed with cyanoacetyl chloride to give 0-cyanoacetylphenylhydrazine 111. In- stead of the acid chloride, cyanoacetazide3can be used, giving a somewhat higher yield. I11 is a colorless well-crystallizing substance.

Homologe des in der vorhergehenden Mittheilung beschriebenen Oxalessigesters lassen sich gewinne, wenn man den Oxalsäureester mit den höreren Fettsäureestern in Reaction bringt.