One-pot synthesis of thieno [2,3-d] pyrimidin-4-ol derivatives mediated by polyphosphonic anhydride

An efficient synthesis of thiopyrimidines with different substituents in position 2 is described. A rapid, mild and high yielding microwave-assisted one-pot cyclization of 5-substituted 2-amino thiophene-3-carboxamide derived from Gewald reaction¹ with T3P and different acids gives the corresponding thiopyrimidines. The significant feature of this method includes less reaction time, high purity and reduced toxicity of the reaction.     

Efficient synthesis of 4-aminoquinazoline and thieno[3,2-d]pyrimidin-4-ylamine derivatives by microwave irradiation

[reaction: see text] A simple, efficient, and high-yielding synthesis of quinazolin-4-ylamine and thieno[3,2-d]pyrimidin-4-ylamine derivatives is reported under microwave irradiation conditions. Reaction conditions including temperature, solvent, and reaction time have been studied. An efficient parallel workup procedure was developed to generate a small library (23 compounds) in a short time period.     

Microwave-assisted synthesis of 2-aminothiophene-3-carboxylic acid derivatives, 3H-thieno[2,3-d]pyrimidin-4-one and 4-chlorothieno[2,3-d]pyrimidine

A two-minute microwave irradiation allowed the synthesis of several 2-aminothiophene-3-carboxylic acid derivatives. Their efficient transformation to thieno[2,3-d]pyrimidin-4-one and the corresponding 4-chloro derivative is also reported under microwave irradiation.     

Solid-phase synthesis of pyrido[2,3-d]pyrimidin-7-ones

A novel solid-phase method for the synthesis of 4-methyl-pyrido[2,3-d]pyrimidin-7-one compounds with two diversity points is described. The polymer supported methylsulfonyl derivatives A₃, achieved by coupling compound G with different resin-bound amines A₁ followed by oxidation with MCPBA, are substituted with several amines R₁R₂NH. Final cleavage affords 126 compounds having formula H in good yield and purity.     

Solid supported synthesis of structurally diverse dihydropyrido[2,3-d]pyrimidines using microwave irradiation

We have synthesized a library of 16 dihydropyrido[2,3-d]pyrimidines in high yields (82-92%) on solid support using microwave irradiation.     

An improved and highly convergent synthesis of 4-substituted-pyrido[2,3-d]pyrimidin-7-ones

A novel and efficient route to 4-substituted-pyrido[2,3-d]pyrimidin-7-ones is described resulting in arrays of compounds with biological interest.     

A convenient synthesis of trisubstituted pyrido[2,3-d]pyrimidin-7-ones

A novel, highly efficient and scalable route for the synthesis of trisubstituted pyrido[2,3-d]pyrimidin-7-ones was developed. The target compounds were synthesized in five steps from readily available reagents in about 40% overall yield.     

Studies on uracils: a facile one-pot synthesis of oxazino[4,5-d]-, pyrano[2,3-d]-, pyrido[2,3-d]- and pyrimido[4,5-d]pyrimidines using microwave irradiation in the solid state

N,N-Dimethyl-5-formylbarbituric acid 1 reacts with maleimide 2 and phenyl isocyanate/phenyl isothiocyanate 4 under microwave-assisted conditions in the solid phase to afford pyrano[2,3-d]pyrimidines 3 and oxazino[4,5-d]pyrimidines 5 in excellent yields. Under identical conditions, N,N-dimethyl-6-amino-5-formyluracil 6 reacts with 2 and 4 to give pyrido[2,3-d]pyrimidine derivative 7 and pyrimido[4,5-d]pyrimidines 8 in high yields.     

A novel synthesis and herbicidal activity of fluorine-containing pyrazolo[3,4-d]pyrimidin-4-one derivatives

The 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio-5-(fluoro-substituted)phenyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-ones 6 have been successfully synthesized via a tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 4, aromatic isocyanate, and substituted phenols 2 in 59-69% isolated yields using actonitrile as solvent. These novel compounds 6 could be oxidized to sulfones 7 by hydrogen peroxide in satisfactory yields (57-93%). Their structures were clearly verified by spectroscopic data (IR, ¹H NMR, ¹³C NMR, MS, Elemental analysis or X-ray diffraction crystallography). The results of preliminary bioassay indicated that these compounds possess herbicidal activity against the root of rape and barnyard grass.     

Efficient approach to the unknown isoxazolo[3,4-d]thieno[2,3-b]pyridine system by regioselective intramolecular nitrone cycloadditions

An effective approach to the new isoxazolo[3,4-d]thieno[2,3-b]pyridine system was provided by way of an intramolecular nitrone cycloaddition. The required nitrones were built in good yields starting from thiophene-2-carboxylic acids. The same skeleton was achieved in optically active form employing chiral nitrones derived from N-α-methylbenzyl- and the N-α-hydroxymethylbenzyl-hydroxylamines. The absolute configuration of the products was assigned by X-ray analysis.     

A novel and efficient synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione and pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives

An efficient and direct procedure for the synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione derivatives has been described under microwave-assisted conditions. Reaction of 6-amino-1,3-dimethyluracil with aromatic aldehydes resulted in the formation of pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives.     

A novel three-component one-pot synthesis of pyrano[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines using microwave heating in the solid state

Microwave-assisted three-component cyclocondensation of barbituric acids 1, benzaldehyde 2 and alkyl nitriles 3 proceeds in the absence or presence of triethylamine to afford pyrano[2,3-d]pyrimidines 4 and 6-aminouracils 5 or 6-hydroxyaminouracils 6 react with 2 and 3 under identical conditions to yield pyrido[2,3-d]pyrimidines 7, all in high yields.     

A novel synthesis of substituted 4H-pyrazolo[3,4-d]pyrimidin-4-ones

A novel synthesis of 4H-pyrazolo-[3,4-d]pyrimidin-4-ones is described. This approach utilizes an in situ generated iminochloride as a key precursor for amidine formation, with subsequent base-catalyzed ring closure. This method represents a mild and efficient entry into this ring system which is amenable to diversification of the core template.     

New iminophosphorane-mediated synthesis of thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes

Mono(iminophosphorane) 4 was selectively prepared from the reaction of 3,4-diaminothieno[2,3-b]thiophene 3 with excess triphenylphosphine, C₂Cl₆, and Et₃N due to intramolecular double hydrogen bond formation. Mono(iminophosphorane) 4 reacted with aromatic isocyanates to give stable carbodiimides 8, which were further treated with aliphatic secondary or primary amines to give 2-amino substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 10 or 12 in the presence of a catalytic amounts of EtO⁻Na⁺. However, in the presence of a catalytic amounts of potassium carbonate, the carbodiimides 8 were transformed into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes 13 via direct cyclization in high yields. The reaction of carbodiimides 8 with phenols in the presence of a catalytic amounts of potassium carbonate gave a mixture of 2-aryloxy substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 14 and 13. X-ray structure analysis of 10m supported the structure and the proposed reactivity of amino group.     

Synthesis of condensed derivatives of 2-substituted thieno[2,3-d]pyrimidin-4-ones

A preparative method of synthesis of 2-substituted thieno[2,3-d]pyrimidin-4-ones involving deamination of the corresponding 3-amino derivatives, by sodium nitrite in acidic medium is proposed. A possible reaction mechanism is considered.A. L. Mndzhoyan Institute of Fine Organic Chemistry. Academy of Sciences of the Republic of Armenia, Erevan 375014 Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 941–944, July, 1999.     

Improved modular synthesis of thieno[3,2-b]pyrroles and thieno[2,3-b]pyrroles

A convenient modular synthesis for the construction of densely functionalized thieno[3,2-b]pyrroles, allosteric inhibitors of the Hepatitis C virus NS5B polymerase, is described. The route allows the introduction of substituents in positions 4, 5, and 6 of the thienopyrrole scaffold and can also be applied to the regioisomeric thieno[2,3-b]pyrrole core.     

Improved synthesis of substituted pyrido[2,3-d]pyrimidinediones

An improved methodology for the synthesis of substituted pyrido[2,3-d]pyrimidinediones from 6-aminouracils and the corresponding enaminone has been developed which provides high yields via an operationally simple process. The method has been extended to encompass a range of electron-rich enaminones, a substrate class that does not perform well under the standard conditions.     

A three-component synthesis of pyrido[2,3-d]pyrimidines

A new, high yield multicomponent reaction providing multifunctionalized pyrido[2,3-d]pyrimidines in a microwave-assisted one-pot cyclocondensation of α,β-unsaturated esters, amidine systems and malononitrile (or ethyl cyanoacetate) is described (the ‘Victory’ reaction).     

Synthesis of thieno[3,4-d]-1,3-dithiol-2-one derivatives

A series of mono-substituted and bis-substituted derivatives of thieno [3,4-d]-1,3-dithiol-2-one were prepared through halogenation, chloromethylation, and subsequent nucleophilic substitution reactions. Compounds were characterized by NMR, FT-IR, and HRMS.     

Design and synthesis of angucyclinone AB-pyrido[2,3-d] pyrimidine analogues

The preparation of two pyrimido[4,5-c]isoquinoline-7,10-quinones from acylhydroquinones and 1,3-dimethyl-5-aminouracil and their cycloadditions with 1-trimethylsilyloxybutadiene and 1-dimethylamino-3-methyl-1-azabutadiene is described. The remarkable regiocontrol of these cycloadditions that yield stable 1:1 cycloadducts is discussed on the basis of steric interactions into the pyrimido[4,5-c]isoquinoline-7,10-quinones. The access to angucyclinone AB-pyridopyrimidine analogues from Diels-Alder adducts and preliminar evidences on their antitumour activities are also reported.