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Efficient and suitable methods for the synthesis of novel class of simple and fused heterocyclic compounds were prepared starting with 1-naphthyl-2-cyanoacetamide and commercially available reagents. The cyclocondensation of 1-naphthyl-2-cyanoacetamide with sulfanylacetic acid furnished phenylthiazolinone derivative. Stirring of the starting compound with PhNCS afforded thiocarbamoyl derivative which underwent heterocyclization with chloroacetyl chloride to give thiazolinone derivative. 5-Aminopyrazole derivative was prepared by following mild procedures via refluxing the last thiocarbamoyl with hydrazine hydrate. Different synthetic approaches were discussed to obtain the novel fused pyrazolo[1,5-a]pyrimidine, 4H-pyrazolo[3,4-d]pyrimidin-4-one moieties involving the reaction of the prepared 5-aminopyrazole with a) 1, 3-dielectrophilic centers (acetylacetone, acetoacetanilide), b) arylidines of malononitrile, and c) isothiocyanate derivatives. The action of iced sodium nitrite solution in acidic medium on the last 5-aminopyrazole gave pyrazolo[3,4-d][1,2,3]triazine. All novel structure were elucidated by different spectroscopic data (IR, MS, 1H, and 13C NMR) and elemental analysis.

The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide in the presence of base in isopropyl alcohol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the novel synthetic methodology for the fused pyrazolopyrimidines.

1,3,4-Thiadiazole-enaminone (6) was synthesized via reaction of the benzamide (5) with DMF-DMA. The simple thiadiazole-enaminone (6) was used as a synthetic precursor for the synthesis of a wide variety of new heterocyclic compounds, including the 5-substituted-1,3,4-thiadiazole derivatives (7), (8), (16), (17) and (18), which were obtained via reactions of (6) with nitrogen nucleophiles. Also, reactions of enaminone (6) with carbon nucleophiles afforded the respective 1,3,4-thiadiazoles (10a,10b). Diazotization of the benzamide (20) with the heteroaromatic amine salts gave the hydrazone derivatives (21) and (22). Cyclization of the latter hydrazones yielded the corresponding pyrazolotriazine and 1,2,4-triazolotriazine derivatives (23) and (24), respectively. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.

5-Amino-3-anilino-1H-pyrazole-4-carbonitrile 1 was alkylated with various halo reagents under phase transfer conditions to give the corresponding imidazopyrazole derivatives 2a, 2b, 2c, 3, 4, 5, 6. Pyrazolo[1,5-a] pyrimidine derivatives 11, 12, 13, 14 were prepared by treating compound 1 with different dicarbonyl reagents, namely, diethymalonate, ethyl 3-oxo-3-phenylpropanoate, pentane-2,4-dione or ethyl 3-oxobutanoate.

Synthesis of ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o-chloroaldehyde 1. Reaction of o-aminocarbonitrile 5 with concentrated H2SO4 furnished expected o-aminocarboxamide pyrazole 6. Key intermediates o-aminocarbonitrile 5 and o-aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o-chlorocarbonitrile 3 with secondary amine furnished new synthon 13, which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, 1H and 13C NMR, and mass spectra.

An efficient synthesis of the hitherto unreported 5-aminopyrazole-4-carboxylate (IV) and its use in the preparation of various pyrazolo [3,4-d] pyrimidine, pyrazolo [1,5-a] pyrimidine and pyrazolylaminotriazole derivatives are described.

1-(β-D-Ribofuranosyl)pyrazolo[3,4-b]pyrimidine-4-thione (6), obtained by a three-step synthesis from allopurinol riboside (3), was treated with certain alkyl and aryl halides to provide the corresponding 4-alkylthio derivatives. The nucleoside 4-methylthio-1-(β-D-ribofuranosyl)pyra-zolo[3,4-d]pyritnidine (7) has served as the precursor for the preparation of the 4-methylamino (11), 4-dimethylamino (12), 4-hydrazino (13), and the 4-hydroxylamino (14) analogs.

The condensation of 4-acetamido-3-cyanopyrazolo[3,4-d]pyrimidine (5) with crystalline 2,3,5-tri-O-acetyl-β-D-ribofuranosyl chloride (6) has furnished a good yield of nucleoside material (7) which on treatment with sodium methoxide in methanol provided a high yield of nucleoside which was subsequently established as methyl 4-amino-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine-3-formimidate monohydrate (11). The formimidate function of 11 was found to be highly reactive and 11 was readily converted into the corresponding carhoxamidine (8), carboxamidoxime (14) and carboxamidrazone (15) when treated with the appropriate nucleophiles. Treatment of the imidate (11) with sodium hydrogen sulfide gave a high yield of the thiocarboxamide (12) which was then readily converted into 4-amino-3-cyano-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (16). Aqueous base transformed 11 into 4-amino-1-(β-D-ribofuranosyl)-pyrazolo[3,4-d]pyrimidine-3-carboxamide (10) while more vigorous basic hydrolysis provided the corresponding carboxylic acid (9) in nearly quantitative yield. Decarboxylation of 9 proceeded smoothly in hot sulfolane to provide the known 4-amino-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (13) in 68% yield which unequivocally established the site of ribosylation and anomeric configuration for all nucleosides reported in this investigation.