Synthesis of Novel Classes of Pyrido[2,3‐d]‐pyrimidines,Pyrano[2,3‐d]pyrimidines,and Pteridines

6‐Amino‐5‐formyluracils 1 and 5‐formyl‐6‐hydroxyuracils 4 react with Meldrum's acid 2 in the presence of piperidine as catalyst under thermolytic conditions to afford 6‐carboxy‐2,4,7‐trioxopyrido[2,3‐d]pyrimidines 3 and 6‐carboxy‐2,4,7‐trioxopyrano[2,3‐d]pyrimidines 5 in good yield. Under identical conditions, 6‐amino‐5‐nitrosouracils 6 react with 2 to afford pteridine‐6‐carboxylic acids 7 in good yields.     

Novel Synthesis of 2‐Oxo‐2H‐Benzopyrano[2,3‐d]Pyrimidines

Abstract

The synthesis of novel substituted 3‐cyanoiminocoumarins and corresponding N‐ethoxycarbonyl iminocoumarins is described. The condensation of N‐ethoxycarbonyl‐3‐cyano‐7‐diethylamino iminocoumarin with amines as N‐nucleophiles yields substituted 2‐oxo‐2H‐benzopyrano‐[2,3‐d]pyrimidines having promising optical properties.     

KF‐Alumina Catalyzed One‐Pot Synthesis of Pyrido[2,3‐d]Pyrimidine Derivatives

Abstract

A series of pyrido[2,3‐d]pyrimidine derivatives was synthesized by the reaction of arylaldehyde, malononitrile, and 4‐amino‐2,6‐dihydroxylpyrimidine in ethyl alcohol at 80°C catalyzed by KF‐Al₂O₃. Compared with other synthetic methods, this new method has the advantage of easier workup, milder reaction conditions, and good yields.     

Three‐Component,One‐Pot Synthesis of Pyrido[2,3‐d]pyrimidine Derivatives Catalyzed by KF‐alumina

Abstract

A series of pyrido[2,3‐d]pyrimidine derivatives were synthesized by the three‐component reaction of arylaldehyde, cyanoacetate, and 4‐amino‐2,6‐dihydroxylpyrimidine in ethyl alcohol at 80°C catalyzed by KF‐Al₂O₃. It was interesting that further aromatization took place automatically. Compared with other synthetic methods, this new method has the advantage of easier workup, milder reaction conditions, and good yields.     

Green Synthesis of Pyrano[2,3‐d]‐pyrimidine Derivatives in Ionic Liquids

Pyrano[2,3‐d]pyrimidine derivatives were synthesized in high yields by a condensation reaction between arylmethylidenemalononitrile and barbituric acid using room‐temperature ionic liquids such as 1‐n‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIm]BF₄) or 1‐butylpyridinium tetrafluoroborate ([BPy]BF₄) as solvents under neutral conditions.     

Synthesis of 2‐Spironaphtho[2,3‐b]pyranoquinones

A convenient procedure for the synthesis of 2‐spirobenzopyranoquinone 5 and its application to the preparation of spironaphtho[2,3‐b]pyranoquinones 6 and 7 is described.     

Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone,a Novel Ring System

A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring.     

Synthesis of Novel Pyrrylthieno[2,3-d]Pyrimidines and Related Pyrrolo[1″,2″:1″,6″]Pyrazino[2″,3″:4,5]Thieno[2,3-d]Pyrimidines

4-Methyl-2-phenyl-5-(1-pyrryl)-6-substituted-thieno[2,3-d]pyrimidines ( 3a-c , 4a-c , 5a , b , and 6 ) have been synthesized. Some of the substituents in position 6 were used to build up different sulfur-, nitrogen- and/or oxygen-containing heterocyclic rings at that position. The 4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide ( 20 ) was also used as a key intermediate in the synthesis of the target pyrrolo[1",2":1',6']pyrazino[2',3':4,5]thieno[2,3-d]pyrimidines.     

Preparation of Nitrogen Heterocycles of Spiro[Furo[2,3‐d]‐Pyrimidine]Pyrimidine Derivatives

Abstract

The NMR evaluation of the reaction progression of the bromination of heterocyclic dibarbiturates was used to develop an efficient synthetic procedure for the preparation of heterocyclic spiro[furo]pyrimidines. The structure of one of these compounds was confirmed by X‐ray analysis.     

Novel Method for Soluble‐Polymer‐Supported Synthesis of 3,4,5‐Trisubstituted Isoxazoles

A practical and efficient liquid‐phase synthesis of 3,4,5‐trisubstituted isoxazoles using poly(ethylene glycol) as supported is described. Soluble‐polymer‐supported nitrile oxide generated in situ reacted with chalcones to afford polymer‐supported isoxazolines, which were cleaved by sodium methoxide to generate 3,4,5‐trisubstituted isoxazoles instead of 3,4,5‐trisubstituted isoxazolines. This sequential process provided a novel method to synthesize 3,4,5‐trisubstituted isoxazoles.     

Synthesis of Novel 5H-1,2,4-Triazolo[5′,1′:2,3] [1,3]Thiazino[5,6-c]Quinoline-5-Ones

4-chloroquinoline-3-carboxylates 2 and 5-mercapto-1,2,4-triazoles 3 have been cyclised to a novel heterocyclic system 4 .     

Simple Analogues of Acyclonucleosides: Synthesis of N‐Substituted Pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine Derivatives

The synthesis of N‐substituted pyridothienopyrimidines bearing ethoxymethyl, benzyloxymethyl, methylthiomethyl, benzoylmethyl, allyl, sec‐butyl, and 2‐acetyloxyethyl chains as a sugar mimic was described. The O‐substituted pyridothienopyrimidines were obtained during some reactions.     

Novel Method for the Synthesis of 6,12‐Dihydro‐2‐Methylindolo[2,3‐ b]Carbazol‐6‐Ones

A novel method for the synthesis of 6,12‐dihydro‐2‐methylindolo[2,3‐b]carbazol‐6‐ones was developed from 1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one through methyl 6‐methyl‐2‐(1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐2‐yl)oxoacetate in good yields. This method provides an alternative path for the synthesis of this product using 2‐hydroxy methylene‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one.     

Synthesis of Fused Tetrazolo[1,5‐c] pyrrolo[3,2‐e]pyrimidines and Their Reductive Conversion to New 4‐Aminopyrrolo[2,3‐d]pyrimidines

Some new 7,9‐substituted 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 1,4‐disubstituted 2‐amino‐3‐cyanopyrroles 1 with formic acid, which, on chlorination using phosphorus oxychloride, afforded 3. 2‐Amino‐3‐cyanopyrroles 1 were synthesized from the reaction between (2-bromo-1-(4-fluorophenyl) ethylidene) propanedinitrile and substituted aromatic amines under Gewald reaction conditions. 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.     

Facile Synthesis of Pyrazolo[3,4‐d]pyrimidines and Pyrimido[4,5‐d]pyrimidin‐4‐one Derivatives

Pyrazolopyrimidine and pyrimidopyrimidine derivatives have shown a wide range of biological activities such as acting as A₁ adenosine receptors, kinase insert domain receptor (KDR), Rous sarcoma oncogene (Src), epidermal growth factor receptor (EGFR), antiproliferative, dihydrofolate reductase (DHFR), antimicrobial, antifungal, and lipid peroxidation. Because of this wide range of activities, we have synthesized pyrazolo[3,4‐d]pyrimidines and pyrimido[4,5‐d]pyrimidin‐4‐one derivatives.     

Synthesis of Some Novel Fluorinated Pyrazolo[3,4‐b]Pyridines

Abstract

Reaction of 5‐amino‐3‐substituted pyrazoles (1a–c) and 5‐amino‐1,3‐disubstituted pyrazoles (1d–i) with fluorinated‐β‐diketones (2) results in the formation of the single isomer of pyrazolo[3,4‐b]pyridines (4a–h). A one‐pot procedure for the synthesis of title compounds starting from α‐cyanoacetophenones along with a possible mechanistic pathway for the formation of the title compounds is described.     

Synthesis of Benzo[b]benzo[2,3‐d]thiophen‐6,9‐diones via Palladium(II) Acetate–Mediated Cyclization of 5‐Arylthiocyclohexa‐2,5‐diene‐1,4‐diones

Palladium(II)‐mediated oxidative cyclization of 5‐arylthiocyclohexa‐2,5‐diene‐1,4‐diones 4 giving biologically important benzo[b]benzo[2,3‐d]thiophene‐6,9‐diones 2 has been performed with a stoichiometric amount of palladium(II) acetate in distillated acetic acid.     

Studies on Thiazolopyridines. Part 1: Antimicrobial Activity of Some Novel Fluorinated Thiazolo[3,2-a]Pyridines and Thiazolo[2′,3′:1,6]Pyrido[2,3-d]Pyrimidines

Ternary condensation of aromatic aldehydes, malononitrile and thioglycolic acid (2:2:1 molar ratio) in ethanol/piperidine afforded the corresponding thiazolo[3,2-a]pyridines 1a-d . Thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 4 was obtained by refluxing of compound 1a with acetic anhydride. Also, thiazolopyrido pyrimidine 6 was produced by refluxing of 1a with triethylorthoformate followed by treatment with hydrazine hydrate. Refluxing 1a with formic acid yielded the thiazolopyridopyrimidine 8 which on chlorination with thionyl chloride furnished the chloro derivative 9 . Finally, amino thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 10 was obtained by treatment of 1a with formamide. The structures of these compounds were established on the basis of elemental analyses, IR, 1 H NMR, and mass spectral data. Also, the antimicrobial activity of some synthesized compounds is reported.     

Pyrido[2,3-d]dipyrimidines 8. Synthesis of pyrrolo(2′,3′∶4,5)pyrido[2,3-d]pyrimidines

The reaction of 1,3-dimethyl-5-chloro-6-nitropyrido[2,3-d]pyrimidine-2,4-dione with CH-acids yielded 5-substituted pyridol[2,3-d]pyrimidines which were used in the synthesis of pyrrolo(2,34,5)pyrido[2,3-d]pyrimidines.For Communication 7, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 800–803, June, 1993.     

Novel Synthesis and Characterization of N‐Substituted‐calix[4]azacrown Derivatives

Novel calix[4]azacrown derivatives from the reaction between calix[4]amidocrown and the different N‐(4‐bromoacetamidephthalimido)alkanes derivatives, which may be useful intemediate compounds of pseudorotaxane, have been synthesized and structurally characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. From their analysis data, it was found that compounds 6a–d adopted a cone conformation.