Pyrido 2,3-d pyrimidines

Appropriate pyrido[2,3-d]pyrimidin-5-ones with formyl groups in the 6-position have been oxiized to piromidic (68) and pipemidic (69) acids, or to intermediates for these, using moist silver oxide, chromium trioxide (potassium dichromate), potassium permanganate or, alternatively, sodium chlorite/hydroxylamine-O-sulfonic acid. 6-Acetyl groups have been similarly oxidized using sodium hypobromite in aqueous dioxane, whilst 2-acetyl groups give dimethylaminomethylene derivatives en route to 2-pyrazolylpyrido[2,3-d]pyrimidines. 

Methanol, l-isoquinolyl(phenyl)-confonnation, 2, 110 Methanol, pyrimidinyl-synthesis, 3, 113 Methanol, tetrahydropyran-2-yl-microwave spectra, 3, 625 Methantheline as neurotransmitter, 1, 175 therapeutic properties, 3, 882 Methaphenilene biological activity, 4, 911 Methapyrilene biological activity, 4, 911 toxicity, 4, 912 Methaqualone, 3, 150 as anticonvulsant, 1, 166 pyrido[2,3-d]pyrimidine analogues metabolism, 3, 205 as sedative, 1, 166 Metharbitone as anticonvulsant, 1, 166 Methazolamide... 

Pyrido[2,3-d]pyrimidine, 2-methylthio-oxidation, 3, 211, 213 Pyrido[2,3-(i]pyrimidine, 7-methylthio-oxidation, 3, 211,... 

Pyrido[2,3-d]pyrimidine-6-carboxylic acid, 5,6,7,8-tetrahydro-5-0x0-synthesis, 3, 221... 

Pyrido[2,3-d]pyrimidine-2-thione, 7-phenyl-reactions, 3, 211 Pyridopyrimidinethiones reactions, 3, 213 Pyrido[2,3-d]pyrimidinethiones reactions, 3, 213... 

The final step in the syntheses of pyrido[2,3-d]pyrimidines from pyridines has involved the formation of the bonds l-8a, 1-2, and 4—4a, but the most useful methods are those which form the 2-3 (i) and 3-4 (ii) bonds. 

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. 

Acid chlorides, acetic anhydride,and formamide have also been used to synthesize pyrido[2,3-d]pyrimidines from 2-ammo-nicotinamides, although in the last case high temperatures were necessary. It is suspected that all the foregoing eyclizations proceed via initial acylation of the 2-amino group to yield an intermediate 2 - amidonicotinamide. 

Only one cyclic hydroxamic acid which contains the pyrido[2,3-d]-pyrimidine ring system has been reported.This is 2-methyl-3-hydroxypyrido[2,3-d]pyrimidin-4(3i/)-one (21) which was prepared by the action of acetic anhydride on 2-aminonieotinhydroxamic acid (20) or from ethyl 2-aeetamidonicotinate (22) and hydroxylamine. In view of the known antibacterial activity of certain cyclic hydroxamic acids further work on these compounds would be of interest. 

Formylation of the amino aldehyde, and subsequent treatment of the amide (46) with ammonia enabled Armarego to prepare pyrido[2,3-d]pyrimidine (1). This compound was also obtained by the decomposition of the tosylhydrazino compound (47). ... 

This is the first synthesis of pyrido[2,3-d]pyrimidines in which both nitrogen atoms of the pyrimidine ring have been supplied by the reagent. In view of the success of similar syntheses of pyrido[4,3-d]-pyrimidines this route would appear to be capable of wide extension. 

The yield of pyrido[2,3-d]pyrimidine has been shown to be significantly reduced when unsubstituted keto aldehydes are used. 

This has been attributed to the self-condensation reactions of these compounds,e.g., acetylacetaldehyde yields s-triacetylbenzene.° Hi. Ethoxymethylene compouTids. Ethoxymethyleneacetoacetates and ethoxymethyleneacetylacetones have been used to prepare pyrido[2,3-d]pyrimidines containing 6-ethoxycarbonyl or 6-acetyl... 

V. Acyl acetates. j8-Keto esters have proved useful for the preparation of pyrido[2,3-d]pyrimidin-7(8H)-ones bearing alkyl and aryl... 

Structural proof has been offered by chlorination, thionation, and reduction to yield the pyrido[2,3-d]pyrimidine (74) which has been subjected to NMR analysis. ... 

Phenylaeetonitrile, ethyl eyanoaeetate, and eyanoaeetamide failed to yield pyrido[2,3-d]pyrimidines. ... 

The 6-methyl derivative (98, R = Me) was an important intermediate in the synthesis of analogs (e.g., 183) of folic acid. Korte has shown that 2-aminopyrido[3,2-guanidine carbonate with 3-aminopicolinic acid and that treatment of the same acid with ammonium thiocyanate or potassium cyanate yields the thioureido and ureido derivatives (100, X = S and X = 0). In contrast to the pyrido[2,3-d]pyrimidine system bsoth of these compounds could be cyclized by heat and the latter (100, X = O) is a likely intermediate in the synthesis of the dione (98) by the fusion with urea. 

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