Synthesis of 4-(trifluoromethyl)pyrido[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

Earlier unknown 4-alkoxy-and 4-hydroxy-5-methyl-4-trifluoromethyl-1,4-dihydropyri-do[4,3-d]pyrimidines were obtained by the reaction of 5-acetyl-4-dimethylaminovinyl-6-(trifluoromethyl)pyrimidine with alcoholic (aqueous) solutions of NH₃. The former eliminate alcohol (water) on sublimation in vacuo to be converted to 5-methyl-4-(trifluoromethyl)-pyrido[4,3-d]pyrimidine. The latter upon the action of alcohols (water) under mild conditions were reverted to the corresponding 4-alkoxy-and 4-hydroxydihydropyrido[4,3-d]pyrimidines.     

New method for the synthesis of thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

The reaction of 5-formyl-4-thiocyanatopyrimidines with nitromethane was studied under various conditions. The reaction was found unexpectedly to proceed with closure of a thiophene ring to give thieno[2,3-d]pyrimidines. The use of ammonium acetate as the catalyst leads to a side reaction involving closure of an isothiazole ring to give isothiazolo[5,4-d]pyrimidines. X-ray diffraction crystallographic analysis was used to confirm the structure of thieno[2,3-d]pyrimidine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1564–1571, October, 2004.     

Alternative Routes to the Pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo-[1,5-<Emphasis Type="Italic">c</Emphasis>]pyrimidine System

Formimidic acid esters derived from 1-substituted 5-aminopyrazole-4-carbonitriles reacted with carboxylic acid hydrazides on heating to give 2,7-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as a result of double heterocyclization. The same compounds were obtained by thermal recyclization of 1-aroyl-2-(1-R-pyrazolo[3,4-d]pyrimidin-4-yl)hydrazines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 934–938.Original Russian Text Copyright © 2005 by Tyurin, Vorob’ev, Minyaeva, Krasnikov, Mezheritskii.     

Transformations of <Emphasis Type="Italic">ortho</Emphasis>-methoxyaryl(hetaryl)carboxamides into quinazolin-4-one and pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4-one derivatives

ortho-Chloroaryl(hetaryl)carboxamides containing one or two nitro groups at positions 3 and/or 5 of the ring undergo condensation accompanied by the pyrimidine ring closure on refluxing in an excess of sodium methoxide to form bicyclic products, viz., quinazolin-4-one, pyrido[2,3-d]pyrimidin-4-one, and pyrido[4,3-d]pyrimidin-4-one derivatives. The scheme of cyclization processes was proposed. The structures of the reaction products were confirmed by a number of physicochemical data, including X-ray diffraction analysis. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1851–1858, August, 2005.     

Construction of a pyrido[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine system on the basis of <Emphasis Type="Italic">N</Emphasis>-cyanobenzamidine and diethyl acetone-1,3-dicarboxylate

Nickel acetate promoted reaction of diethyl acetone-1,3-dicarboxylate with N-cyanobenzamidine led to ethyl 4-amino-6-ethoxycarbonylmethyl-2-phenylpyrimidine-5-carboxylate, upon treatment of which with RNH₂, the corresponding 6-(carbamoylmethyl)pyrimidines were obtained. Cyclization of the latter upon treatment with MeONa afforded 6-R-4-amino-7-hydroxy-2-phenylpyrido[4,3-d]pyrimidin-5(6H)-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2212–2214, November, 2007.     

Reactions of 3-allyl-4-oxothieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-2-yl disulfides with iodine

Reactions of 3-allyl-4-oxothieno[2,3-d]pyrimidin-2-yl disulfides with iodine afforded 2-iodomethyl-2,3-dihydrothieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-ones. A probable mechanism of this transformation was theoretically justified. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2501–2504, November, 2005.     

Fluorinated [1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines and [1,2,4]triazolo[5,1-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazines*

The reaction of 3-R-5-amino-1,2,4-triazoles with the ethyl ester of 2-fluoroacetoacetic acid gave 2-R-fluoro[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-ones. The reaction of a 3-R-1,2,4-triazolyl-5-diazonium salt with the ethyl ester of 2-fluoroacetoacetic acid and subsequent cyclization of the triazolylhydrazones lead to 7-R-3-fluoro[1,2,4]triazolo[5,1-c][1,2,4]triazin-4(1H)-ones.     

4,5-Diamino-1-phenyl-1,7-dihydro-6<Emphasis Type="Italic">H</Emphasis>-pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridin-6-one in the synthesis of fused tricyclic systems

Starting from the substituted 4,5-diaminopyrazolo[3,4-b]pyridine, derivatives of a number of tricyclic systems, viz., imidazo[4,5-d]pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b][1,2,5]thiadiazolo[3,4-d]pyridine, pyrazolo[3,4-b][1,2,3]triazolo[4,5-d]pyridine, and [1,3]oxazolo[5,4-b]pyrazolo[4,3-e]pyridine, were synthesized and reaction schemes for the processes were proposed.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]-1,2,4-triazolo[4,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-5-ones

Abstract  The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species. Graphical abstract        

Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]-pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones with arenesulfenyl chlorides

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ were accompanied by intramolecular electrophilic cyclization involving the N⁷ atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′: 5,6]pyrimido[2,1-b][1,3]thiazine derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system reduces the yield of the corresponding intramolecular cyclization product at N⁷ as a result of concurrent formation of acyclic addition product. DOI     

Pyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidinium salts

5-Aroyl-1,3,6-trimethyluracils were converted to pyrano[4,3-d]pyrimidinium salts. Reactions of the salts obtained with ammonia, primary amines, and hydrazine were studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2251–2257, November, 2007.     

Synthesis and properties of pyrimido[4,5-<Emphasis Type="Italic">a</Emphasis>]- and pyrido[4,3-<Emphasis Type="Italic">a</Emphasis>]carbazole derivatives

Methods for the synthesis of substituted pyrimido [4,5-a]- and pyrido[4,3-a]carbazoles were proposed. Condensation of 2-(dimethylaminomethylene)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one with guanidine and thiourea afforded 2-amino-8-methyl-6,11-dihydro-5H-pyrimido[4,5-a]carbazole and 8-methyl-3,5,6,11-tetrahydro-2H-pyrimido[4,5-a]carbazole-2-thione, respectively. The reaction of cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide with dimethylformamide dimethyl acetal gave N-(dimethylamino-methylene)cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide. Cyclization of the latter yielded 1-cyano-8-methyl-3,5,6,11-tetrahydro-2H-pyrido[4,3-a]carbazol-2-one.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2740–2744, December, 2004.     

Synthesis of pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-7(8<Emphasis Type="Italic">H</Emphasis>)-one derivatives from 5-acetyl-4-aminopyrimidines and β-dicarbonyl compounds

Heating of 5-acetyl-4-aminopyrimidine derivatives with ethyl acetoacetate, ethyl benzoylacetate, and diethyl acetone-1, 3-dicarboxylate in the absence of a base gave the corresponding 6-acylpyrido[2, 3-d]pyrimidin-7(8H)-ones. Under analogous conditions, the reaction with ethyl malonate afforded ethyl 7-oxo-7, 8-dihydropyrido[2, 3-d]pyrimidine-6-carboxylates. The pyridone (rather than hydroxypyridine) structures of the pyridopyrimidines obtained were confirmed by IR spectroscopy.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 770–773, March, 2005.     

Fused Pyrimidine Systems: XVII. Imidazo- and Pyrimidopyrido[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

2-(Allylamino)pyrido[3,2-d]pyrimidin-4(3H)-one was converted to linearly fused dihydroimidazo- [1,2-a]pyrido[3,2-d]pyrimidine on heating in polyphosphoric acid, whereas its reactions with molecular iodine and chlorosulfanylarenes afforded mainly angularly fused analogs. 2-(Cinnamylamino)pyrido[3,2-d]pyrimidin- 4(3H)-one reacted with polyphosphoric acid and chlorosulfanylarenes to give linear pyrido[3,2-d]pyrimido-[1,2-a]pyrimidinones, and its iodocyclization led to the formation of angularly fused derivative.     

Pyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidinium salts

Reactions of 5-aryl- and 5,7-diaryl-1,3-dimethyl-2,4-dioxopyrano[4,3-d]pyrimidinium salts with hydrazine were studied. In the former case, the reaction products were the 6-amino-1,3-dimethyl-2,4-dioxopyrido[4,3-d]pyrimidinium salts. 5,7-Diarylpyrano[4,3-d]pyrimidinium salts were transformed into either the corresponding pyridinium salts or 1H-pyrimido-[5,4-d][1,2]diazepine-2,4(3H,9H)-diones, depending on the hydrazine concentration and the reaction time. For Part 1, see Ref. 1. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1720–1725, May, 2008.     

Synthesis and functionalization of 7-hydroxyanthra[2,1-<Emphasis Type="Italic">b</Emphasis>]benzo[<Emphasis Type="Italic">d</Emphasis>]furan-8,13-diones

The diazotization of 1-amino-2-aryloxy-4-hydroxy-9,10-anthraquinones in various solvents and subsequent heating of the diazotization products lead to 7-hydroxyanthra[2,1-b]benzo[d]furan-8,13-diones. When consecutively treated with benzenesulfonyl chloride and amines, the products form 7-aminoanthra[2,1-b]benzo[d]furan-8,13-diones.     

Synthesis of 7-oxopyrrolo-[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidine 5-oxides by the rearrangement of 6-alkynyl-5-nitropyrimidines

A method is proposed for the synthesis of 6-substituted 4-amino-7-oxopyrrolo[2,3-d]pyrimidine 5-oxides which includes a Sonogashira reaction of 4-amino-6-chloro-5-nitropyrimidine with terminal alkynes and subsequent rearrangement of the 6-alkynyl-5-nitropyrimidines obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10. pp. 1546–1550, October, 2004.     

Transformations of tetrahydro-pyrido[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines [<Emphasis Type="Italic">b</Emphasis>]-condensed with isoxazole,thiazole, thiadiazole,and triazole units under the action of activated alkynes

It has been established that 5-vinyl-substituted (N-R,N-vinylaminomethyl)isoxazolo(thiazolo, thiadiazolo)pyrimidines are formed when tetrahydropyrido[3,4-d]pyrimidines, annelated with isoxazole, thiazole, and thiadiazole units are treated with terminal alkynes as a result of opening of the tetrahydropyridine ring. 7-Methoxymethyl-substituted [N-R,N-(dimethoxycarbonylvinyl)]aminoethyl-isoxazolo- and thiazolopyrimi-dines were obtained by reaction with dimethyl acetylenedicarboxylate (ADCE). Triazolo-pyrimidoazocine was obtained for the first time from tetrahydrotriazolopyrimidine and methyl propiolate. Dedicated to Academician B. A. Trofimov on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, 1861–1872, December, 2008.     

Tandem transformations of tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines under the action of dimethyl acetylenedicarboxylate. A novel route to pyrrolo[2,3-<Emphasis Type="Italic">d</Emphasis>]azocines

Reactions of substituted tetrahydropyrrolo[3,2-c]pyridines with dimethyl acetylenedicarboxylate in protic and aprotic solvents were studied. A novel single-step method for the synthesis of pyrrolo[2,3-d]azocine derivatives was developed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2513–2519, November, 2005.     

Reaction of 2-alkylthio-6-amino-pyrimidin-4(3H)-ones with ethyl bromopyruvate. Synthesis of furo-[2,3-<Emphasis Type="Italic">d</Emphasis>]-pyrimidine and furo[3,2-<Emphasis Type="Italic">e</Emphasis>]imidazo-[1,2-<Emphasis Type="Italic">c</Emphasis>]pyrimidine carboxylates

Reaction of 2-alkylthio-6-aminopyrimidin-4(3H)-ones with ethyl bromopyruvate to give ethyl 2-alkyl-thio-4-aminofuro[2,3-d]pyrimidine-5-carboxylates has been shown to proceed under neutral or acidic conditions. The obtained furo[2,3-d]pyrimidines underwent further cyclocondensation reaction with ethyl bromopyruvate to afford diethyl 5-alkylthiofuro[3,2-e]imidazo[1,2-c]pyrimidine-2,9-dicarboxy-lates. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 440–443, March, 2009.