Synthesis of pyrrolo[2,3-d]pyrimidines with 3-amino-2-hydroxypropyl substituents

A novel route has been found for the synthesis of pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines. They are promising reagents for the preparation of pyrrolo[2,3-d]pyrimidine-6-carboxylic acid amides which contain a 3-amino-2-hydroxypropyl substituent in position 7 of the heterocyclic ring.     

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).     

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.     

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.     

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.     

Synthesis of substituted 2-amino-3-cyanopyrroles

A method was worked out for the preparation of substituted 2-amino-3-cyanopyrroles from N-acyl-α -amino ketones and malononitrile. Acyl derivatives of 2-amino-3-cyanopyrroles were obtained. A number of Mannich bases were synthesized by aminomethylation of 2-acetamido-3-cyano-4-phenylpyrrole.     

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.     

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.     

Syntheses of substituted pyrrolo[2,3-d]imidazoles

Starting from the readily available 5-hydroxymethyl-2-mercapto-1-methylimidazole (1) substituted pyrrolo[2,3-d]imidazoles were prepared.     

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.     

Halogenation of some substituted 3-allyl-2-mercapto-3,4-dihydrothieno[2,3-d]pyrimidines

The bromination and iodination of substituted 3-allyl-2-mercapto-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidines have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1289–1290, September, 1973.     

Synthesis of substituted 3,4-dihydrofuro[2,3-d]pyrimidines from 3-arylmethylidenefuran-2(3H)-ones

Russian Journal of Organic Chemistry -     

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.     

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:...     

Novel animation reactions of dihydrofurano[2,3-d] pyrimidines

Although alkoxypyrimidines can be aminated to yield aminopyrimidines, monoamination of 2,4- or 4,6-chloroalkoxypyrimidines results in chlorine displacement. Preferential alkoxy displacement in such systems is unusual. We now have evidence of such a displacement in the dihydrofurano[2,3-d] pyrimidines (V). In some cases two types of products, formed by displacement of either the chlorine or alkoxy substituent, were obtained.     

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 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.     

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 .