Synthesis and reactions of fluoroaryl substituted 2-amino-3-cyanopyrroles and pyrrolo[2,3-d]pyrimidines

Some fluoroaryl substituted 2-amino-3-cyanopyrroles 2 were synthesized from the reaction between (2-bromo-1-arylalkylidene)propanedinitriles 1 and fluoroaryl substituted aromatic amines under Gewald reaction condition, which on reaction with formamide and formic acid gave 4-aminopyrrolo[2,3-d]pyrimidines 3 and pyrrolo[2,3-d]-pyrimidin-4(3H)-ones 4 respectively. 4-Chloropyrrolo[2,3-d]pyrimidines 5 were prepared by chlorination of 4 with phosphorus oxychloride, which on hydrazinolysis provided 4-hydrazinopyrrolo[2–3-d]pyrirnidines 6 .     

Synthesis of pyrrolo[2,3-d]pyrimidines (microreview)

Chemistry of Heterocyclic Compounds - Microreview summarizes recent methods for the synthesis of pyrrolo[2,3-d]pyrimidines, published since 2015. The methods are classified as Cu-catalyzed...     

Synthesis of thiopyrano[2,3-d] pyrimidines and thieno[2,3-d]pyrimidines

The reaction of 4-chloro-5-cyano-2-methylthiopyrimidine (I) with ethyl mercaptosuccinate (II) in refluxing ethanol containing sodium carbonate has afforded diethyl 3-amino-2-(methyl-thio)-7H-thiopyrano[2,3-d]pyrimidine-6,7-dicarboxylate (IV). Displacement of the methylthio group in IV with hydrazine gave the corresponding hydrazino derivative which underwent Schiff base formation with benzaldehyde or 2,6-dichlorobenzaldehyde. Treatment of IV in refluxing acetic anhydride afforded the corresponding diacetylated amino derivative. Partial saponification of IV with sodium hydroxide gave 5-amino-2-(methylthio)-7H-thiopyrano-[2,3-d]pyrimidine 6,7-dicarboxylic acid 6 ethyl ester (VIII). The reaction of 4-amino-6-chloro-5-cyano-2-phenylpyrirnidine (XI) with II resulted in the formation of ethyl 4-amino-6-(ethoxy-carbonyl)-5,6-dihydro-5-amino-2-phenylthieno[2,3-d]pyrimidine-6-acetate (XIII) which when subjected to hydrolysis gave ethyl 4,5-diamino-2-phenylthieno[2,3-d]pyrimidine-6-acetate isolated as the hydrochloride (XIV). Diazotization of IV with sodium nitrite in acetic acid unexpectedly afforded diethyl 5-(acetyloxy)-6,7-dihydro-6-hydroxy-2-(methylthio)-5H-thio-pyrano[2,3-d]pyrimidine-6,7-diearboxylate (XV). Several structural ambiguities were resolved by ir and pmr spectra.     

Solid-phase synthesis of tetrasubstituted pyrrolo[2,3-d]pyrimidines

A facile solid phase synthesis of 2,4,6,7-tetrasubstituted pyrrolo[2,3-d]pyrimidines is described. The synthesis involves a highly efficient five-step route starting from resin-bound dimeric peptoids. To demonstrate the versatility of our method, a representative library of 108 tetrasubstituted pyrrolo[2,3-d]pyrimidines of high quality was synthesized.     

Synthesis,anticancer and antimicrobiological activities of pyrrolo[2,3-d]pyrimidines

Reactions of 6-amino-3,4-dihydro-2-methoxy-4-oxopyrimidine 1a and its 3-methyl derivative 1b with chloroacetaldehyde and chloroacetyl chloride are discussed in this paper. Amongst others compounds, we have obtained, in low yield, the novel ring system oxazolo[3,2-c]pyrrolo[3,2-e]pyrimidine. The anticancer and antimicrobial activities of some of the obtained products are described.     

Pyrido[2,3-d]pyrimidines. 2. Reactions of 2,4,5-trioxo-7-amino-8H-pyrido[2,3-d]pyrimidines with electrophilic agents

1,3-Dimethyl-2,4,5-trioxo-7-amino-8H-pyrido[2,3-d]pyrimidine has been brominated, chlorosulfonated, treated with potassium nitrite in acidic medium, and with the Vilsmeier reagent. Acylation and alkylation of 1,3-dimethyl-2,4,5-trioxo-6-bromo-7-aminopyrido[2,3-d]pyrimidine is also discussed.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 662–666, May, 1990.     

Pyrido[2,3-d]pyrimidines. 1. Acylation of 2,4,5-trioxo-7-amino-8H-pyrido [2,3-d]pyrimidines

Reaction of 2,4,5-trioxo-7-aminopyrido[2,3-d]pyrimidines with acylating agents takes place both at the amino group and at the cyclic nitrogen atom. Reaction of these compounds with formic acid, chloroacetyl chloride in pyridine, cyanoacetic acid in the presence of acetic anhydride, and oxalyl chloride leads to monoacylation at the amino group but with methyl chloroformate it is the product of acylation at the cyclic nitrogen. Refluxing in acetic anhydride gave mono-, di-, and triacetyl derivatives. The structures of these compounds were proved using spectral data.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 811–814, June, 1990.     

Facile synthesis of 1-substituted 2-amino-3-cyanopyrroles: new synthetic precursors for 5,6-unsubstituted pyrrolo[2,3-d]pyrimidines

1-Benzyl-3-cyanopyrrole-2-carbonyl azide (5) underwent a Curtius rearrangement followed by quenching with alcohols to form the corresponding carbamates (6a-c). The carbamates 6a,b were unblocked to give the desired 2-amino-1-benzyl-3-cyanopyrrole (1a). A more facile procedure was subsequently developed for the synthesis of 1-substituted 2-amino-3-cyanopyrroles. N-Substituted aminoacetaldehyde dimethyl acetals (7a-c) were condensed with malononitrile in the presence of p-toluenesulfonic acid monohydrate to afford the corresponding 1-substituted 2-amino-3-cyanopyrroles (1a-c).     

Pyrrolo[2,3-d] pyrimidines. I. 5-hydroxypyrrolo[2,3-d] pyrimidines

5-Hydroxy-7-alkyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitriles (VIIb-d) and 5-hydroxy-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid, ethyl ester (VIIa) were prepared from 5-carbethoxy-4-chloro-2-phenylpyrimidine (IV) via 4-[(cyanomethyl)alkylamino[-2-phenyl-5-pyrimidinecarboxylic acid, ethyl esters (Vb-d) and 4-[(carboxymethyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid, diethyl ester (Va), respectively. The hydroxy group of the pyrrolo-[2,3-d]pyrimidines could be methylated, acetylated and tosylated. Hydrolysis of 5-methoxy-7-methyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitrile (IX) afforded the corresponding amide (X).     

Synthesis of pyrido[2,3-d]pyrimidines from 6-amino-1,3-dimethyluracil and aldehydes

Russian Journal of Organic Chemistry - 6-Amino-1,3-dimethyluracil reacted with aliphatic aldehydes on heating in formic acid to give mixtures of 1,3,7,9-tetramethylpyrido[2,3-d:...     

Synthesis of 3-amino-1-benzyl-4-benzenesulfonyl-2-carbonitrilo-1H-pyrrole and preparation of related pyrrolo[3,2-d]pyrimidines

A method for the synthesis of a new 4-phenylsulfonyl-substituted 3-aminopyrrole was developed and related pyrrolo[3,2-d]pyrimidine derivatives were synthesized.     

Synthesis of new 6-Aroylpyrido[2,3-d]pyrimidines

The synthesis of 6-dimethylaminomethylenaminopyrimidin-4(3H)-ones 2 and its reaction with β-dimethyl-aminopropiophenone hydrochloride 3 is discussed in this work. The reaction of 6-aminopyrimidin-4(3H)-ones 1 with an excess of dimethylformamide dimethyl acetal gives rise to the formation of 6-dimethylaminomethyleneaminopyrimidines 2. The heating of equimolecular quantities of 2 and 3 in dimethylformamide leads to the 6-aroylpyrido[2,3-d]pyrimidines derivatives 4. The structures of compounds 2 and 4 were determined on the basis of nmr measurements.     

Synthesis of pyrido[2,3-d]pyrimidines from aminopyrimidinecarbaldehydes

2-Methoxy-4-amino-5-pyrimidinecarbaldehyde ( 2a ) as well as its 6-methyl 2b and 6-phenyl derivatives 2c were prepared by reduction of the corresponding aminopyrimidinecarbonitriles 1 . Catalytic hydrogenation of 1a, 1b gives 5-hydroxymethylpyrimidines 3a, 3b ; under the same conditions 1c afforded 5-aminomethylpyrimidine 4 . Condensation of 2 with carbonitriles, ketones and polyfunctional carbonyl compounds bearing the -CH₂CO- moiety afforded the pyrido[2,3-d]pyrimidines and pyrimido-[4,5-b]quinoline derivatives.     

Synthesis and structural study of novel 5-aryl substituted 2-amino-4,7-dioxopyrido[2,3-d]pyrimidines

The tide compounds 4a-c have been prepared in a one-step procedure from 2,4-diamino-6-hydroxy-pyrimidine (1) and the corresponding arylidene substituted Meldrum's acids 2a-e in very good yields. Semiempirical theoretical calculations (AMI) reveal two favoured conformations ( A and B ) for compounds 4a-e. The ¹H-nmr determinations, by using Karplus and Altona equations, clearly indicate that conformation A, with the aryl group on C5 in a pseudoaxial position, is that predominant in solution. The calculated charge density values for the olefinic carbons are in agreement with the experimental push-pull effect observed in the ¹³C-nmr spectra.     

The synthesis and transformations of 3-ethoxycarbonyl-2-isothiocyanatopyridine. Pyrido[2,3-d]pyrimidines and some azolopyrido[2,3-d]pyrimidines

3-Ethoxycarbonyl-2-isothiocyanatopyridine ( 2 ), prepared from 2-amino-3-ethoxycarbonylpyridine ( 1 ) by the thiophosgene method, was converted into thiouretanes 3 and 4 , 1,4-disubstituted thiosemicarbazide 6 , thioamide 8 , and thioureas 15 and 18 . The compounds 2 and 3 were converted into bicyclic pyrido[2,3-d]pyrimidines 5, 9, 10, 11, 12, 16 , and 17 , and tricyclic azolopyrido[2,3-d]pyrimidines 13 and 14 .     

Synthesis of New 3-Carboxamidine Iminocoumarins and Benzopyrano[2,3-d]pyrimidines

A new approach to synthesis of a series of 3-carboxamidine iminocoumarins derivatives and substituted benzopyrano[2,3-d]pyrimidines was developed. The chemical structure of all the compounds was investigated by infrared, ¹H NMR, ¹³C NMR, mass, and elemental analysis. The anticholinesterase activity of compound 12 was evaluated according to the modified Ellman’s method.     

Synthesis of 7H-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines and their reductive ring cleavage to 4-aminopyrrolo[2,3-d]pyrimidines

Some new 7,9-disubstituted 7H-1,2,3,4-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines 5 have been synthesized either by diazotization of 4-hydrazino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 4 obtained by hydrazinolysis of 4-chloro-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 3 or via a substitution reaction between 3 and sodium azide. 5,7-Disubstituted-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-ones 2 were obtained by cyclocondensation of 2-amino-3-cyano-1,4-disubstituted pyrroles 1 with formic acid which on chlorination using phosphorus oxychloride afforded 3 . A novel route for the synthesis of 4-amino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 6 by the reductive ring cleavage of 5 has been reported.     

Synthesis of furo[2,3-d]pyrimidines condensed with a tetrahydrothiopyran

Using o-iodobenzoic acid we synthesized 5-hydroxy-2,2-dimethyltetrahydrothiopyran-4-one. From the latter we synthesized 2-amino-5,5-dimethyl-3-cyano-4,5-dihydro-7H-furo[2,3-c]thiopyran; this is a starting material for the preparation of furo[2,3-d]pyrimidine condensed with tetrahydrothiopyran and triazole rings.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1403–1405, October, 1990.     

An efficient synthesis of pyrrolo[2,3-d]pyrimidines via inverse electron demand diels-alder reactions of 2-amino-4-cyanopyrroles with 1,3,5-triazines

The scope of the inverse electron demand Diels-Alder reaction of 2-amino-4-cyanopyrroles (3a-e) with 1,3,5-triazines (1, 2) is reported. This methodology is suitable for one-pot syntheses of highly substituted and highly functionalized pyrrolo[2,3-d]pyrimidines that are the central heterocyclic nucleus of various nucleoside natural products such as toyocamycin, sangivamycin, and tubercidin.     

Pyrido[2,3-d]pyrimidines 4. Synthesis and some transformations of oxo(hydroxy)pyrido[2,3-d]pyrimidines

The cyclization of 5-cyanoacetyl-6-aminouracils in acidic media was accomplished. The structures of the pyrido[2,3-d]pyrimidines obtained and their properties are discussed.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 674–680, May, 1991.