Synthesis of pyrazolo[3,4‐d]pyrimidine derivatives using ketene dithioacetals

Abstract

The cyclization of 5‐amino‐3‐methylthiopyrazole‐4‐carbonitriles or 4‐carboxamides 3a‐j, which were prepared by the reaction of ketene dithioacetals 1a,b [1a: bis(methylthiomethylenemalononitrile; 1b: bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p‐chlorophenylhydrazine, p‐nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4‐amino‐ or 4‐hydroxy‐3‐methylthiopyrazolo[3,4‐d]pyrimidines 6a‐h in good yields. 3‐Aminopyrazolo[3,4‐d]pyrimidine derivatives 6i‐1 were also obtained by the application of the cyclization reaction of 3,5‐diaminopyrazoles with formamide.

Synthesis, Characterization and In Vitro Antitumor Evaluation of New Pyrazolo[3,4-d]Pyrimidine Derivatives

“…The resulting 2(bis(methylthio)methylene)malononitrile was then treated with phenyl hydrazine in absolute ethanol [17]. Cyclization of the 5-amino-3-(methylthio)-1-phenyl-1Hpyrazole-4-carbonitrile (7) by the action of formic acid afforded 3-(methylthio)-1-phenyl-1H-pyrazolo [3,4-d]pyrimidin-4(5H)-one [18].…”

“…Progress of the reactions were monitored by TLC pre-coated with UV fluorescent silica gel and was visualized using UV lamp and different solvent systems as mobile phases. 5-Amino-3-(methylthio)-1-phenyl-1H-pyrazole-4-carbonitrile (7) and 3-(methylthio)-1-phenyl-1H-pyrazolo [3,4-d]pyrimidin-4(5H)-one (8) were prepared according to published method 17 . Compound 9 was obtained following reported procedure [19].…”

Recent developments in the field of A3 adenosine receptor antagonists

“…In particular, from comparison of compound 73 with the corresponding C 9 unsubstituted 32 (Table 2), it was shown that the introduction of the small lipophylic methylsulfanyl moiety at C 9 position determined a dramatic shift of binding affinity from hA 3 to the hA 2A subtype, reversing the effect of the ureidic chain at the N 5 position. As depicted in Schemes 1 and 2 the introduction of a substituent at the C 9 position was possible using malononitrile (Scheme 1, a) as the starting material, which, reacting with carbon disulfide and methyliodide in presence of K 2 CO 3 and anhydrous DMF, provided the 2-(bis methylsulfanilmethylene)-malononitrile (b) in good yield [Tominaga et al, 1990]. The subsequent reaction with methylhydrazine in ethanol gave the 1-methyl-3-amino-5-methylsulfanl-4-cyano-pyrazole (c), which was treated, as described in Scheme 1, according to the well-known procedure for the synthesis of the pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidines, previously reported [Baraldi et al, 1996a], to furnish final compounds 76-78, 73.…”

Synthesis, antimicrobial activity and absorption studies of some novel heterocyclic dyes based on 4-hexylbenzene-1,3-diol

“…The usage of many pyrazole derivatives has undoubtedly created considerable attention in developing many different synthetic procedures in pharmaceuticals, agrochemicals, dyestuff. The recent developments in the synthetic routes and the chemistry of pyrazoles have been thoroughly reviewed [1][2][3][4][5]. The condensation of β-enaminonitriles and β-ketoesters with hydrazines continues to be the most widely used method for constructing the aminopyrazoles and pyrazolones, respectively [6,7].…”