Synthesis and properties of substituted 1-aryl-1,4-dihydro-4-oxopyrido[2,3-d]-pyrimidines

The reaction of 2-arylamno-6-methylnicotinonitriles with acetic anhydride or benzoyl chloride gives N-acyl-2-arylamino-6-methylnicotinonitriles. Upon treatment with hydrogen chloride in anhydrous ethanol, these products are converted to 2-substituted 1-aryl-1,4-dihydro-7-methyl-4-oxopyrido[2,3-d]pyrimidines. Heating amides of 2-aryl-amino-6-methylnicotinic acids or 1-aryl-2,7-dimethyl-1,4-dihydro-4-oxopyrido[2,3-d]-pyrimidines at reflux with acetic anhydride in the presence of anhydrous sodium acetate gives 1-aryl-2-acetonyl-7-methyl-1,4-dihydro-4-oxopyrido[2,3-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 114–116, January, 1985.     

Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Synthesis of 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-one derivatives

This paper reports the synthesis of new pyrido[2,3-d]pyrimidin-4-one derivatives as diuretic agents. Starting with 1,2-dihydro-5-nitro-2-oxo-3-pyridinecarboxylic acid 1 , ethyl 2-ethoxy-5-nitro-3-pyridincarboxylate 4 was obtained. Compound 4 reacts with ammonia, methylamine or S-methylpseudothiourea to give the respective 2-amino-5-nitro-3-pyridinecarboxamide derivatives 5 and 6 or 2-methylthio-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-one 8. Treating carboxamide 5 with arylaldehydes and zinc dichloride, new 2-aryl-1,2-dihydro-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-ones 9 were synthetised. These compounds reduced with iron(II) hydroxide gave 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-ones 10 as expected.     

Synthesis and properties of 2-substituted 1-aryl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines

Cyclization of 2-(N-acetyl-N-arylamino)nicotinonitriles in the presence of dry HCl gave 1-aryl-2-methyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines. It was shown that they are acylated by acetic anhydride, aroyl chlorides, and phenyl isocyanate at the methyl group and that with benzaldehyde they give styryl derivatives. It was determined by UV, IR, and NMR spectra that 2-acetonyl, 2-phenacyl, and 2-(N-phenylcarbamoylmethyl) derivatives of 1-aryl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines exist in enaminocarbonyl and imino enol forms with strong chelate-type intramolecular hydrogen bonding.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1397–1401, October, 1991.     

Synthesis and properties of 1-aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines

1-Aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines are formed from the cyclization of N-acetyl-2-arylamino-4,6-dimethylnicotinonitriles by perchloric acid in a mixture of acetic acid and acetic anhydride. 1-Aryl-2-acetonyl-5,7-dimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines areformedonheating2-arylamino-4,6-dimethylnicotinamides with acetic anhydride. These and analogous compounds were obtained by acylation of 1-aryl-2,5,7-trimethyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines with acetic anhydride or benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1234–1236, September, 1992.     

Synthesis and Properties of Ethyl Esters of 4-Dialkylamino-2-methylthiothieno[2,3-d]pyrimidine-6-carboxylic Acids

The reaction of 4-dialkylamino-6-chloro-2-methylthiopyrimidine-5-carbaldehydes with ethyl mercaptoacetate in the presence of triethylamine gives the corresponding ethyl esters of thieno[2,3-d]pyrimidine-6-carboxylic acids. These esters were subjected to alkaline hydrolysis, hydrazinolysis, and lithium aluminum hydride reduction to give the corresponding acids, hydrazides, and (thieno[2,3-d]pyrimidin-6-yl)methanols.     

Synthesis of 8-cyano-1,4-dihydro-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylic acids as potential antimicrobial agents

The preparation of a variety of 8-cyano-1,4-dihydro-7-phenyl-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylicacids and 8-cyano-1,4-dihydro-7-p-fluorophenyl-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylic acids is described.     

Synthesis of 1,4-dihydro-4-oxopyridazino[1,6-a]indole-3-carboxylic acids and 1,4-dihydro-4-oxopyrido[3′,2′:4,5]pyrrolo[1,2-b]-pyridazine-3-carboxylic acids as potential antibacterial agents

A few aza analogues of the quinolones have been prepared in the two families of the 1,4-dihydro-4-oxopyridazino[1,6-a]indole-3-carboxylic acids and the 1,4-dihydro-4-oxopyrido[3′,2′:4,5]pyrrolo[1,2-b]-pyridazine-3-carboxylic acids to check their antibacterial potential. One compound 6c shows antibacterial activities of the level of nalidixic acid and represents a new lead structure differing from the classical quinolones.     

Synthesis of 1,4-dihydro-4-oxopyrrolo[1,2-b]pyridazine-3-carboxylic acids and 1,4-dihydro-4-oxoimidazo[1,5-b]pyridazine-3-carboxylic acids as potential antibacterial agents

To check the antibacterial potential of two families of aza analogues of the quinolones, 1,4-dihydro-4-oxopyrrolo[1,2-b]pyridazine-3-carboxylic acids and 1,4-dihydro-4-oxoimidazo[1,5-b]pyridazine-3-carboxylic acids, we have prepared a few derivatives in theses families using N-aminopyrrole and N-aminoimidazole derivatives as starting building blocks and the classical pathways of the quinolone series. The compounds showed no interesting antibacterial activity.     

Thieno[2,3-d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3-d] pyrimidine-6-carboxylic acids

A novel method for the preparation of esters and amides of thieno[2,3-d]pyrimidine-6-carb-oxylic acids was described. A typical example was the direct formation of ethyl 5-amino-2-methylthiothieno[2,3-d]pyrimidine-6-earboxylate(IIIa) from 4-chloro-2-methylthio-5-pyrimidine-carbonitrile (Ia) and ethyl mercaptoacetate in refluxing ethanol containing sodium carbonate. Displacement of the methylthio group in IIIa by various amines gave the corresponding amino derivatives. The reactions of IIIa and related compounds with acetylating agents such as acetic anhydride or chloroacetyl chloride gave various products. Treatment of 5-carbethoxy-4-chloro-2-phenylpyrimidine(IV) with methyl mercaptoacetate afforded the dechloro intermediate diester Va, which cyclized on reaction with sodium ethoxide to form methyl 5-hydroxy-2-phenylthieno-[2,3-d]pyrimidine-6-carboxylate (Vla). The synthesis was expanded to include the preparation of various new 2,4,5-trisubstituted thieno[2,3-d]pyrimidine-6-carboxylic acid esters and amides (Charts I-V).     

Synthesis of derivatives of 2-oxo-2,3-dihydro-1H-thieno[3,4-d]imidazole

Conclusions Derivatives of 2-oxo-2,3-dihydro-1H-thieno[3,4-d]imidazole were synthesized from 4,5-di-substituted 2-imidazolinones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2381–2383, October, 1987.     

Pyrido[2,3-d]pyrimidines 3. Synthesis and properties of 7-chloro- and 6-nitro-7-chloropyrido[2,3-d]pyrimidine-2,4,5-triones

7-Chloropyridopyrimidine was obtained by diazotization of 1,3-dimethyl-7-amino-8H-pyrido[2,3-d]pyrimidine-2,4,5-trione in HCl, and its nitration and reactions with nucleophilic reagents were studied. An imidazo[1,2:1, 6]pyrido[2,3-d]pyrimidine derivative was synthesized.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 497–501, April, 1991.     

Synthesis of 5-amino derivatives of ethyl 2-methylthiothieno-[2,3-d]pyrimidine-6-carboxylate and their reaction with hydrazine

A study has been made of the reaction of the ethyl esters of 5-amino-, 5-ethoxy-methyleneamino-, and 5-acetylamino-2-methylthiothieno[2,3-d]pyrimidine-6-carboxylic acids with hydrazine. Certain derivatives of 3-aminothieno[2,3-d4,5-d']-dipyrimidin-4(3H)-ones have been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1131–1134, August, 1987.     

Synthesis of Pyrano[2,3-d]pyrimidine-2,4-diones and Pyridino[2,3-d]pyrimidine-2,4,6,8-tetraones: Evaluation Antitumor Activity

A series of some novel pyrano[2,3-d]pyrimidine 4 – 10 with 75–95% yields and pyridino[2,3-d]pyrimidine derivatives 11 – 16 with 75–92% yields is reported. The building structures have been achieved by reaction of 5-arylidene barbituric acid 2 and active nucleophile carbon or nitrogen as examples barbituric acid and acetyl acetone or refluxing of bispyrimidine-2,4,6-trione derivative 3 with cyclizing reagents such as phosphorous pentoxide, hydrazine hydrate and aminothiazole. The newly synthesized structures have been elucidated on the basis of their spectral analysis. Some selected members were screened for antitumor activity. Among the screened compounds 9 , 16 , 7 , 10 and 8 exhibited high antitumor activity.     

Efficient method for the synthesis of novel substituted thieno[2,3-d]pyrimidine-4-carboxylic acids,their derivatization,and antimicrobial activity

Chemistry of Heterocyclic Compounds - An effective method for accessing novel substituted thieno[2,3-d]pyrimidine-4-carboxylic acids in 63–71% yields based on Pd(dppf)Cl2-catalyzed...     

Synthesis of pyrido[2,3-d]pyrimidin-4-one derivatives

This paper describes one-pot synthesis of 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidin-5-one 4 , 5H-dipyri-do[1,2-a:3′,2′-e]pyrimidin-5-one 10 and 5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one 15 and some of their derivatives, starting with 2-chloro-3-pyridine carboxilic acid 1. Compounds 4 and 10 reacted with phosphorus pentasulfide to give the respective 5-thione analogues, 5 from 4 and 11 from 10 . Boiling the 5-thione derivatives with hydrazine hydrate, the respective 5-hydrazono derivatives 6 from 5 and 12 from 11 were obtained. The 5-acetyl hydrazono, 7 , and the 5-isopropylidenehydrazono, 8 , derivatives were also prepared from 6 , and the 5-propionylhydrazono derivatives, 13 , from 12 . Compound 4 reacted with hydrazine to give an adduct with two molecules of hydrazine and the probable structure 16 . Treating this adduct with acetone a monohydrazone 17 was obtained. Boiling a suspension of this adduct in DMF, it gave 6,10-dihydro-6H-pyrido[3′,2′:5,6]pyrimido[2,1-c][1,2,4]triazin-5-one 20 .