Synthesis and properties of 2-amino-4,6-dimethylnicotinic acid arylamides

It is shown that on boiling 2-amino-4,6-dimethylnicotinic acid arylamides with triethyl orthoformate in acetic anhydride, derivatives of 3-aryl-5,7-dimethyl-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidine are formed. The same compounds are obtained by ternary condensation of ethyl 2-amino-4,6-dimethylnicotinate with triethyl orthoformate and alrylamines. On reaction with urea or ammonium thiocyanate, the ethyl ester or anilides of 2-amino-4,6-dimethylnicothinic acid are converted to 2,4-dioxo- or 4-oxo-2-thio-pyrido[2,3-d]pyrimidines respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1384–1386, October, 1992.     

Synthesis and properties of 2-substituted 1-aryl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines

Cyclization of 2-(N-acetyl-N-arylamino)nicotinonitriles in the presence of dry HCl gave 1-aryl-2-methyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines. It was shown that they are acylated by acetic anhydride, aroyl chlorides, and phenyl isocyanate at the methyl group and that with benzaldehyde they give styryl derivatives. It was determined by UV, IR, and NMR spectra that 2-acetonyl, 2-phenacyl, and 2-(N-phenylcarbamoylmethyl) derivatives of 1-aryl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines exist in enaminocarbonyl and imino enol forms with strong chelate-type intramolecular hydrogen bonding.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1397–1401, October, 1991.     

Synthesis and properties of substituted 1-aryl-1,4-dihydro-4-oxopyrido[2,3-d]-pyrimidines

The reaction of 2-arylamno-6-methylnicotinonitriles with acetic anhydride or benzoyl chloride gives N-acyl-2-arylamino-6-methylnicotinonitriles. Upon treatment with hydrogen chloride in anhydrous ethanol, these products are converted to 2-substituted 1-aryl-1,4-dihydro-7-methyl-4-oxopyrido[2,3-d]pyrimidines. Heating amides of 2-aryl-amino-6-methylnicotinic acids or 1-aryl-2,7-dimethyl-1,4-dihydro-4-oxopyrido[2,3-d]-pyrimidines at reflux with acetic anhydride in the presence of anhydrous sodium acetate gives 1-aryl-2-acetonyl-7-methyl-1,4-dihydro-4-oxopyrido[2,3-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 114–116, January, 1985.     

Synthesis and properties of 1-aryl-1,4-dihydro-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidine-6-carboxylic acids and their derivatives

Acetylation of 2-arylamino-5-carbethoxy-6-methylnicotinonitriles gave N-acetyl-2-arylamino-5-carbethoxy-6-methylnicotinonitriles, which, under the influence of hydrogen chloride, are cyclized to 1-aryl-1,4-dihydro-6-carbethoxy-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidines. The latter can be converted to the corresponding carboxylic and hydroxamic acids, as well as to acetylation products 1-aryl-2-acetonyl-1,4-dihydro-6-carbethoxy-7-methyl-4-oxopyrido [2,3-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535–539, April, 1992.     

Synthesis of Derivatives of 4,6-Dioxo-1,4,6,7,8,9-hexahydropyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>][1,6]naphthyridines

It has been shown that 1-aryl-8-(4-bromophenyl)-4,6-dioxo-2H(phenyl)-7-phenyl-1,4,6,7,8,9-hexahydropyrimido[4,5-b][1,6]naphthyridines are formed on heating anilides of 1-aryl-7-(4-bromostyryl)-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acids in PPA.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 597–600, April, 2005.     

Reactions of 6-Amino-5-Cyano-3-Methyl-1,4-Diphenyl-1H 4H-Pyrano[2,3-C]Pyrazole and its Methanimidate

Reaction of 6-amino-5-cyano-3-methyl-1,4-diphenyl- 1H,4H-pyrano[2,3-c]pyrazole 1 with triethyl orthoformate in acetic anhydride gave its methanimidate 2, which reacts with primary aliphatic and aromatic amines to give 4,6-dihydro-3-methyl-1,4-diphenyl-6- (alkyl)pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5(lH)- imine 3 and the starting compound 1 , respectively. Treatment of 1 with o-aminophenol gave 5-(2-benzoxalyl)- 1,4-dihydro-3-methyl-1,4-diphenylpyrano[2,3-c]pyrazol- 6-amine 9.     

Synthesis of new pyrido[2,3-d]pyrimidine derivatives

The mutual condensation of 4-aminouracil or 2,4-diamino-6-hydroxypyrimidine with bisacetonitrile and aldehydes was used to synthesize 2,4-dioxo-5-R-7-methyl-6-cyano-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4,5,8-tetrahydropyrido[2,3-d]pyrimidine derivatives, which were oxidized with chromic anhydride to the corresponding 2,4-dioxo-5-R-7-inethyl-6-eyano-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4-dihydro[2,3-d]pyrimidines. The IR and UV spectra of the synthesized compounds were recorded.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 422–425, March, 1972.     

Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Condensed isoquinolines 32. Synthesis of 4H-thieno-[3′,2′:5,6]-and-[2′,3′: 5,6]pyrimido-[1,2-b]isoquinolines and 6,12-dihydro-5H-isoquino-[2,3-a]quinazoline-5,12-dione derivatives

Treatment of 2-(4-oxo-3,4-dihydrothieno[2,3-d]-and-[3,2-d]pyrimidin-2-ylmethyl)benzoic acids and 2-(4-oxo-3,4-dihydro-2-quinazolinylmethyl)benzoic acid with acetic anhydride gave thieno[3′,2′:5,6]-and-[2′,3′:5,6]pyrimido[1,2-b]isoquinoline-4,11-diones and isoquino[2,3-a]quinazoline-5,12-dione respectively. NMR spectroscopy showed that an intramolecular acylation of the above acids occurs at the atom N-1 of the pyrimidinone part of the bicycle. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1053–1061, July, 2008.     

Synthesis of amino derivatives of triazolopyrimidine

Heterocyclization of 1-(4,6-dimethylpyrimidin-2-yl)-4-R-thiosemicarbazides by the action of methyl iodide in ethanol in the presence of sodium acetate is accompanied by Dimroth rearrangement leading to the formation of 5,7-dimethyl-2-R-amino[1,2,4]triazolo[1,5-a]pyrimidines. Analogous heterocyclization of 4-aryl-1-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thiosemicarbazides gives 3-arylamino-7-methyl-5-oxo-[1,2,4]triazolo[4,3-a]pyrimidines. The presence in the pyrimidine ring of a carbonyl group capable of forming hydrogen bond with protons of the amino group stabilizes the molecule, thus hampering the Dimroth rearrangement.     

Synthesis and reactivity of 3-amino-9-methoxymethyl-7-methyl-3,4-dihydropyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones

The reaction of acyl derivatives of ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate with hydrazine hydrate gives a series of tricyclic 3-amino-3,4-dihydropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones containing aliphatic, aromatic, or heteroaromatic fragments at C₍₂₎. The reactions of 3-aminopyridothieno[3,2-d]pyrimidin-4-ones with aldehydes, formamide, 2,5-dimethoxytetrahydrofuran, acetic anhydride, and Raney nickel were studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1720–1732, November, 2007.     

Condensed pyridazines. Part III. Rearrangement and ring cyclization during the thermolysis of (z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-methylacrylate

The thermolysis of (Z)-methyl 3-(6-azido-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazin-5-yl)-2-methylacrylate ( II ) provides a new synthetic route to pyrrolo[2,3-c-]pyridazines, specifically, methyl 3-chloro-1,6-dimethyl-4-oxo-1,4-dihydro-7H-pyrrolo[2,3-c]pyridazine-5-carboxylate ( III ) in 91% yield. Treatment of III with ozone provides an entry into the novel pyridazino[3,4-d][1,3]oxazine ring system, specifically, 3-chloro-1,7-dimethylpyridazino[3,4-d][1,3]oxazine-4,5-dione ( IV ) in 73% yield. Compound IV is smoothly hydrolyzed into 6-acetylamino-3-chloro-1-methyl-4-oxo-1,4-dihydropyridazine-5-carboxylic acid ( V ) which is readily recyclized into IV by dehydration with acetic anhydride. Furthermore, IV undergoes a facile reductive ring opening reaction with sodium borohydride to give 3-chloro-6-ethylamino-1-methyl-4-oxo-1,4-dihydropyridazine-5-carboxylic acid ( VI ) in 95% yield.     

A convenient synthesis for some new pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine derivatives with potential biological activity

Ready, convenient synthesis for 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-1,2,3,-4-tetrahydropyrido-[3′,2′:,4,5]thieno[3,2-d]pyrimidines 5 , 8-cyano-7-ethoxy-4-oxo-9-phenyl-2-substituted-3,4-dihydropyrido[3′,2-: 4,5]thieno[3,2-d]pyrimidines 6 , 4-chloro-8-cyano-7-ethoxy-9-phenyl-2-substitutedpyrido[3′,2′:4,5]thieno[3,2-4 -pyrimidines 7 and 8-cyano-7-ethoxy-2-(2′-nitrophenyl)-9-phenyl-4-substitutedpyrido[3′,2′:4,5]thieno[3,2- d ]pyrimidines 8-18 from 2-chloro-3,5-dicyano-6-ethoxy-4-phenylpyridine 1 via 3,5-dicyano-6-ethoxy-2-mercapto-4-phenylpyridine 2 and aminocarboxamide 4 are reported. In addition, the reaction of hydrazino derivative 12 with reagents such as formic acid and triethyl orthoformate yielded the fused tetraheterocyclic 8-cyano-9- ethoxy-5-(2′-nitrophenyl)- 7-phenylpyrido[3′,2′:4,5]thieno[2,3-e]-1, 2,4-triazolo[4,3-c]pyrimidine system 19 .     

Synthesis and reactions of 2-substituted 1-phenyl-4-oxo-1,4-dihydropyrido-[2,3-d]pyrimidines

2-Methyl-4-oxo-1-phenyl-1,4-dihydropyrido[2,3-d]pyrimidine was acylated by succinic and trifluoroacetic anhydrides and also underwent the Claisen reaction with diethyl oxalate and ethyl oxanilate to give acyl derivatives at the methyl group, which, according to UV, IR, and¹H NMR spectra, exist as enaminocarbonyl and iminoenol tautomers with intramolecular hydrogen bonds.Perm State Pharmaceutical Academy, Perm 614600, Russia. e-mail: GIO@pharm.perm.su. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1119–1122, August, 2000.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1- b ]quinazolin-9-one Derivatives

 A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives.     

Acetals of lactams and acid amides. 40. Synthesis and hydrolytic cleavage of one-ring and two-ring derivatives of 4-pyrimidinone

The reaction of 1-benzyl-5-cyano-6-dimethylaminomethylene-1, 6-dihydro-4-pyrimidinone with acid leads to 5-benzyl-1,2,7,8-tetrahydropyrido[4,3-d]pyrimidine-1,8-dione, whereas the reaction with ammonia leads to a mixture of 3-cyano-4-benzylamino-2-pyridone and 1-amino-5-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. Heating of the latter in aqueous ethylene glycol is accompanied by recyclization to give 4-benzylamino-5,6-dihydropyrido[2,3-d]pyrimidin-5-one. The reaction of 1-benzyl-4-ditnethylaminomethylene-5-cyano-1,6-dihydro-6-pyrimidinone with ammonia leads to 1-amino-7-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. The rate constants for cleavage of the pyrimidine ring in a number of 4-pyrimidinone derivatives were measured.See [1] for communication 39.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 532–537, April, 1984.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1-b]quinazolin-9-one Derivatives

Summary.  A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives. Received March 22, 2001. Accepted (revised) May 11, 2001     

Synthesis of 2-aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones by reaction of 2-benzylamino-1,4-naphthoquinones with nitric acid

2-Aryl-1-hydroxy-1H-naphtho[2,3-d]imidazole-4,9-diones were synthesized by treatment of 2-benzylamino-1,4-naphthoquinones with a mixture of nitric and sulfuric acids in acetic acid.     

Synthesis of New Derivatives Benzo[4′,5′]imidazo[2′,1′:6,1]pyrido[2,3-d]pyrimidine

Russian Journal of Organic Chemistry - The reactions of 4-methyl- and (RS)-4,6-dimethyl-2-phenyl-5,6-dihydrobenzo[4′,5′]imidazo-[2′,1′:6,1]pyrido[2,3-d]pyrimidines and...