New efficient route to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines via regioselective cross-coupling reactions

The first access to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines III is reported. Two mild alternative routes led to the rarely targeted compounds from 2,4-dichloro- and 2-chloro-4-isopropylsulfanyl-pyrido[3,2-d]pyrimidine by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. These results open the way to innovative synthesis strategies of various bis-functionalized pyrimidine series.     

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

2-Ethoxycarbonyl-3-isothiocyanatopyridine ( 2 ), prepared from 3-amino-2-ethoxycarbonylpyridine ( 1 ) by the thiophosgene method, was converted with nucleophiles into pyrido[3,2-d]pyrimidine derivatives 6–11 and 25–30 either directly, or through thiourethane 3 . Tricyclic systems 18 and 19 were obtained from 3 , and tricyclic systems 12–17 from pyrido[3,2-d]pyrimidine derivative 11 . Pyrrole reacted with 2 at C₂ to give 20 , and by further cyclization 21 and 22 .     

Syntheses of functionalized thieno[3,4-d]imidazoles and thieno[3,2-d]pyrimidines from chlorine-containing enamidonitriles

Enamidonitriles of the general formula Cl(X)C=C(CN)NHCOR readily react with methyl sulfanylacetate to give tri-or tetra-substituted thiophenes, which can be converted into new functional derivatives of thieno[3,2-d]pyrimidine and thieno[3,4-d]imidazole.     

Diversity-oriented synthesis of functionalized pyrrolo[3,2-d]pyrimidines with variation of the pyrimidine ring nitrogen substituents

Nine 2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid benzyl esters 12 were synthesized in four steps from 4-oxo-N-(PhF)proline benzyl ester 7 by a general method in which elements of molecular diversity were readily added onto the pyrimidine nitrogens. Conversion of 4-oxoproline 7 into the corresponding aminopyrrole 8 using benzyl-, allyl-, and isopropylamine followed by treatment with phenyl, allyl, and ethyl isocyanate gave nine different ureas 9. 4-Ureido-1H-pyrrole-2-carboxylic acid benzyl esters 9 were then converted into the respective pyrrolo[3,2-d]pyrimidines 12 using trichloroacetyl chloride in acetonitrile followed by treatment with Cs(2)CO(3). Crystallization from toluene gave the desired deazapurines in 37-55% overall yield from proline 7.     

Synthèse des pyrido[2,3-d] el [3,2-d] -s-triazolo[3,4-f] pyrimidines el de (pyrazolyl-1')-4 pyrido[2,3-d] et [3,2-d] pyrimidines

The synthesis of two new heterocycles is described: pyrido-[2,3-d]-.s-triazolo[ 3,4-f] pyrimidine and pyrido[3,2-d]-.s-triayzolo-[3,4-f] pyrimidine. 4-[I'-Pyrazolyl]pyrido[2,3-d]pyrimidines and 4-[1′-pyrazoly1] pyrido[ 3,2-d] pyrimidine are obtained by the action of 4-hydrazinopyrido[2,3-d]pyrimidine and 4-hydrazinopyrido-[3,2-d]pyrimidine with several β-diketones.     

New syntheses of pyrido[3,2-d]pyrimidines

New synthetic routes to pyrido[3,2-d]pyrimidines starting with 5-amino-1,3,6-trimethyluracil (I) or 1,3,6-trimethyl-5-nitrouracil (X) are described. Thus, condensation of I with arylaldehydes gave 5-arylideneamino-1,3,6-trimethyluracils (IIa-h), which upon heating with dimethylformamide dimethylacetal afforded 6-aryl-1,3-dimethylpyrido[3,2-d]pyrimidine-2,4(1H,3H)-diones (Va-h) via 5-arylideneamino-1,3-dimethyl-6-(2-dimethylaminovinyl)uracils (IIIa-h). On the other hand, reaction of X with phenylacetaldehyde in the presence of base yielded Va and its 5-oxide (XI).     

A new synthesis of benzofuro[3,2-c]pyridines

The condensation of O-phenylhydroxylamine with piperidin-4-one and 3-methylpiperidin-4-one has given 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine and 4-methyl-1,2,3,4-tetrahydro-benzofuro [3,2-c]pyridine, and these have been dehydrogenated to the corresponding heteroaromatic system of benzofuro[3,2-c]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.7, pp. 908–909, July, 1973.     

The synthesis of benzofuroquinolines. I. Some benzofuro[2,3-b]quinoline and benzofuro[3,2-c]quinoline derivatives

Benzofuro[2,3-b]quinoline ( Ia ) and its 11-methyl derivative ( Ib ) were synthesized by demethylcyclization of 3-(o-methoxyphenyl)-1,2-dihydroquinolin-2-ones (VIa,b). Benzofuro[2,3-b]quinoline-11-carboxylic acid (Id) was synthesized by chlorination followed by the action of potassium hydroxide of a lactone (IX) prepared by demethyl-cyclization of 3-(o-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-4-carboxylic acid (VIII). Isomeric benzofuro[3,2-c]quinoline (Ha) and its 6-methyl derivative (IIb) were synthesized by demethyl-cyclization of 3-(o-methoxyphenyl)-1,4-dihydroquinolin-4-ones (XIa,b). Both the methyl derivatives (Ib and IIb) were converted to the carboxylic acids (Id and IId) through condensation with benzaldehyde followed by oxidation. The benzofuroquinolines (Ia,b,d and IIa,b) thus obtained were oxidized to the corresponding N-oxides (IIIa,b,d and IVa,b).     

Studies on the synthesis of 2-(2-arylvinyl)thieno[2,3-d]pyrimidines and 5-(2-arylvinyl)triazolothieno[3,2-e]pyrimidines

Synthesis of 2-(2-arylvinyl)thienopyrimidines, by the acid catalyzed condensation of nitriles with thiophene o-aminocarbonyl compounds, the condensation of aldehydes with thiophene o-aminoamides, the base catalyzed condensation of aldehydes with 2-methylthienopyrimidines and by the Wittig condensation of 2-thieno-pyrimidinylmethylphosphonium salts with aldehydes is described. Isomeric 5-methyltriazolothienopyrimidines were found to react, under basic condition, with aldehydes yielding 5-(2-arylvinyl)triazolo[2,3-c]thieno-pyrimidines. While 5-styryltriazolo[4,3-c] isomers resisted acid catalysed isomerization, they were found to isomerize to triazolo[2,3-c]pyrimidines under base catalysis.     

Synthesis of New Fused Thieno[3,2-d]pyrimidines Based on Thieno[3,2-d][1,3]oxazine Derivative

Russian Journal of General Chemistry - A method was developed for the synthesis of new fused amines, thieno[3,2-d]pyrimidine derivatives, starting from the corresponding chloride and various...     

One-pot Synthesis of 2,4-Diamino-substituted Thieno[3,2-d]pyrimidines

An efficient one‐pot synthetic approach to 2,4‐diamino‐substituted thieno[3,2‐d]pyrimidines from 2,4‐dichlorothieno[3,2‐d]pyrimidine was described.     

Electroorganic synthesis of new benzofuro[2,3-d]pyrimidine derivatives

Electrochemical oxidation of 3,4-dihydroxybenzoic acid (1) in the presence of 1,3-dimethylbarbituric acid (2) and 1,3-diethyl-2-thiobarbituric acid (3) as nucleophiles in aqueous solution has been studied using cyclic voltammetry and controlled-potential coulometry. The results indicate that 1 via Michael reaction under electro-decarboxylation reaction converts to benzofuro[2,3-d]pyrimidine derivatives (6a, 6b). The electrochemical synthesis of 6a, 6b has been successfully performed in an undivided cell in good yields and purity.     

Au(I)-catalyzed efficient synthesis of functionalized bicyclo[3.2.0]heptanes

An efficient Au(I)-catalyzed synthesis of highly strained and functionalized bicyclo[3.2.0]heptanes is developed. Subsequent couplings with various nucleophiles offer additional structural features/complexity. These one-pot, three-component reactions are proposed to proceed via a key 1,3-dipolar cycloaddition between a Au carbenoid-containing carbonyl ylide and ethyl vinyl ether.     

An efficient regioselective synthesis of highly functionalized 3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidines via an isocyanide-based three-component reaction

We present a novel, convenient, and efficient method for synthesizing polysubstituted 3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidines via a three-component reaction. The zwitterions generated from the reaction of isocyanides and dialkyl acetylenedicarboxylates react with 2-imino-1,3-thiazolidin-4-one to produce the title compounds in good yields.     

An efficient one-pot three-component synthesis of functionalized pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-d]pyrimidines in water

A simple, efficient, and high yielding one-pot protocol for the synthesis of pyrimido[4,5-b]quinolines and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidines has been developed by three-component domino coupling of 6-amino-1,3-dimethyluracil, aldehydes, and cyclic 1,3-diketones in ecofriendly solvent water promoted by PTSA. The protocol avoids the use of expensive catalysts, toxic solvents, and chromatographic separation. The generality and functional tolerance of this convergent and environmentally benign method is demonstrated.     

Regioselective synthesis of pyrido[2,3-d]pyrimidines

The reaction of diethyl ethoxymethylenemalonate ( 1 ) and 6-amino-1,3-dimethyluracil ( 2 ) was determined to be regioselective. Under acidic conditions the product was the previously isolated 7-oxopyrido[2,3-d]pyrimidine ( 3 ), while in the presence of one equivalent of base followed by thermal cyclization, the isomeric 5-oxopyrido[2,3-d]pyrimidine ( 5 ) is formed.     

Some reactions of 4-aminopyrazolo[3,4-d]pyrimidines

New 3-bromo and 1,4-diaminomethyl derivatives of 4-aminopyrazolo[3,4-d]pyrimidine were obtained by bromination and aminomethylation, respectively. 4-Bromopyrazolo[3,4-d]pyrimidines were synthesized for the first time by diazotization of 4-aminopyrazolo[3,4-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 982–984, July, 1982.     

5-Acetyl-6-amino-4-methylthio-2-phenylpyrimidine and its use in the synthesis of functionalized pyrido[2,3-d]pyrimidines and pyrimido-[4,5-d]pyrimidines

Schemes for the synthesis of MeS-substituted pyrido[2,3-d]pyrimidin-5-one, pyrimido[4,5-d]pyrimidine, and 4-methylenepyrimido[4,5-d]pyrimidin-2-one based on 5-acetyl-6-amino-4-methylthio-2-phenylpyrimidine, which was prepared from the adduct of benzoyl isothiocyanate with acetylketeneN-benzoylaminal, were suggested.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1324–1328, July, 1995.The work was carried out with financial support from the Russian Foundation for Basic Research (Grant No. 94-03-08964).     

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.