2-Aryl-6-substituted-4/7-pyrido

A number of 8-aryl substituted pyrido[3,4-t/]-l,2,3-triazin-4(3//)-ones have been found to be most efficacious as inhibitors of xanthine oxidase, potential compounds for the treatment of ischemia and gout <88EUP274654>. A number of 3//,4//-pyrido[3,2-e]-l,2,4-triazine and 3/f,4//-pyrido[3,4-e]-1,2,4-triazine 3-acetamides have shown antiinflammatory, diuretic, antihypertensive, and psychotropic effects <89FES279>. During a search for potential antidepressant compounds, the pyrido-1,2,3-triazinone (399) was found to be more active than its isomer (400) <87EJM337>. 

Cyclocondensation of ethyl 2-aminonicotinate in presence of HC(OEt)3 and various primary amines gave 22 3-substituted pyrido[2,3-,7]pyrimidin-4(377)-ones 371 <1995PHA719>. Fourteen 3,5,7-triarylpyrido[2,3-r7]pyrimi-dine-2,4(l/7,37/)-diones 372 have been prepared from the reaction of either 2-amino-3-cyano-4,6-diarylpyridines or the 3-carboxamido products of alcoholic KOH hydrolysis, with aryl isocyanates better yields were obtained from the amides <1995IJB740>. 4-Aminopyrido[2,3- pyrimidin-5(8//)-one 158 was synthesized by treatment of 2-amino-3-cyano-4-methoxypyridine with trimethylsilyl iodide to give the corresponding pyridin-4(177)-one, which was refluxed with formamidine acetate in ethoxyethanol to effect the cyclization <2000JME3704>. 

Eight examples of 3-aryl pyrido[3,2-e]-1,2,4-triazines were prepared via a reductive cyclization route. Thus, 3-phenylpyrido[3,2-e]-l,2,4-triazine (65) was prepared from the aminopyridine (234) by cyclization followed by oxidation <76CR(C)487>. In another study, seven 3-substituted pyrido-1,2,4-triazines were prepared via an analogous route <76MI 717-04). This work mirrored the earlier investigations of Lewis and Shepherd <7lJHC4l>. 

It was, however, impossible to obtain /V-alkyl or N-aryl substituted 1,3-benzaza-phospholes or pyrido-anellated 1,3-azaphospholes through the above route. However, palladium-catalyzed cross coupling, followed by reduction of the resulting o-ani-lino- or o-arninopyridophosphonates and condensation with dimethylformamide dimethylacetal led to the desired TV-substituted benzazaphospholes (36, X = CH) or pyrido-anellated azaphospholes (36, X = N) (Scheme 11) [43 47],... 

In a similar manner,benzo[6]pyrido[3,2 [l,4]oxazepinones 115 were prepared using a ligand-free, copper-catalyzed process (14RA55640). An intramolecular 1,3-dipolar cycloaddition reaction of 6-azido-4-0-propargyl glucopyranosides generated aryl-substituted hexahydro-4H-pyrano[2,4 [l,2,3]triazolo[5,l-c][l,4]oxazepines 116 (14RA63962). 

Tu and coworkers reported a new and highly stereoselective four-component protocol for the domino reaction of 2,6-diaminopyrimidine-4-one 153 with structurally diverse aryl aldehydes 69 and various barbituric acids 156, resulting in 6-spiro-substituted pyrido[2,3-d]pyrimidines 157 and 158 with high diastereoselectivity (up to 99 1), in which the major diastereomer bears a cis relationship between the substituents at the 5- and 7-positions (Scheme 12.63) [87]. 

Zohuri et al. (2013) synthesized novel 2,9-dihydro-2-oxo-4-aryl-l//-pyrido[2,3-fc] indole-3-carbonitrile derivatives by condensation of substituted (triethoxymethyl) arene, l-methyl-lH-indol-2-ol, and cyanoacetamide using catalytic amounts of crosslinked poly(2-acrylamido-2-methyl propane sulfonic acid) (AMPS) as an efficient and heterogeneous catalyst (Scheme 2.10). This polymeric solid acid catalyst is stable and can be easily recovered and reused without significant change in its... 

Aryl-substituted benzotriazoles and their pyrido-fused analogues 99 were obtained via copper(I)-catalyzed intramolecular cyclization of 2-haloaryltriazenes 98 in aqueous solution of PEG 400 (Scheme 54) [85]. It should be... 

The use of substituted 2-aminonicotinio acids has enabled a series of pyrido[2,3-d]pyrimidines, which have 5-, 6-, and 7-alkyl and aryl substituents, to be obtained. 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution by the presence of electron-donating substituents at the 2- and 4-positions undergo cyclization. 2,4,6-Triaminopyrimidine, 6-aminouracil, 6-amino-2-thiouracil, 4-amino-2,4 dimercaptopyrimidine, 2,4-diaminopyrimidin-6(l/I)-one, and various 4-amino-vV-alkyl and aryl pyriinidones have all been converted into pyrido[2,3-[Pg.160]

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

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