4-hydroxy-6-methyl-2 -pyridone

N-Methyl-4-hydroxy-2-quinolone 183 in a three-component reaction gives spiro pyrano[3,2-c]qionoline-2-ones (02MI2), but indolones 213 with 4-hydroxy-6-methyl-2-pyridone 177 react in a complicated way (97BCJ1625). Ethoxycarbonyl-methylene indolone (Z = COOEt) forms pyrans 224, while dicyano analogs (Z = CN) yield substituted quinoline 225 (Scheme 85). 

Condensation of 4-hydroxy-6-methyl-2-pyridone with isobutylglyoxal in MeOH containing NaOMe yields quantitatively the Na salt of 155. Its diacetate,... 

Diketene and glycine in a basic solution ve 3-acetyl-1-carboxymethylene-4-hydroxy-6-methyl-2-pyridone (XII-189) by a reaction path in which dehydroacetic acid is not an intermediate. However, W-acetoacetylglycine was not detected. Deacylation of XII-189 to XII-190 occurs in sulfuric acid. 

Dehydroacetic acid oxime rearrangesinpolyphosphoricacidto 3-acetamid04 hydroxy-6-methyl-(2ff)-2-pyrone and 2,6-dimethyl-(4 0 Pyrano[3,4-d] oxazol-4-one (W-242). Treatment of W-242 with ammonia gives 2,6-dimethyl-(5//)-oxazolo[4,5-c]-4-pyridone, which, in turn, gives 3-acetamido4-hydroxy-6-methyl-2-pyridone with hydrochloric acid at room temperature and 3-amino-4-hydroxy-6-methyl-2-pyridone on heating. ... 

Reactions between triacetic acid lactone (MI-243) and ammonia or amines to give 4-hydroxy-6-methyl-2-pyridones are well known. For example, glycine and XII-243 give l-carboxymethylene-4-hydroxy-6-methyl-2-pyii-done. This latter 4-hydroxy-2-pyridone has also been formed from diketene and glycine in aqueous base via XU-244, which can be deacetylated in concentrated sulfuric acid. Dehydroacetic acid does not appear to be an intermediate in the formation of xn-244. Under these conditions it reacted with glycine to form an isomeric product, which, however, was not characterized. ... 

Acetylacetone and malonyl chloride give 5-acetyl-4-hydroxyd-methyl-2-pyrone (XII-253), a positional isomer of dehydroacetic acid, which reacts with aqueous ammonia or aqueous methylamine to form XII-254 (R = H, CHs), which can also be prepared from the enamine of acetylacetone and carbon suboxide (see Section I.3.E., p. 635). The //-methylpyridone XII-2S4 (R = CH3) is deacetylated to 4-hydroxy-l,6-dimethyl-2-pyridone with sulfuric acid however, W-254 (R = H) was not deacetylated under these conditions. Acetylacetone and carbon suboxide give 8-acetyl-4-hydroxy-7-methylpyrano-[4,3-6] pyiane-2,5-dione (XI-255) with catalytic amounts of sulfuric acid. This is also formed from acetylacetone and malonyl chloride or from carbon suboxide and the intermediate 5-acetyl-4-hydroxy-6-methyl-2-pyrone (XU-253). 3,5-Diacetyl-4-hydroxy-6-methyl-2-pyrone (XI-256) can be formed by acetylation of XII-253 with acetic acid and phosphorus oxychloride or by degradation of XII-255. 3,5-Diacetyl-4-hydroxy-6-methyl-2-pyridone can... 

The 4-hydroxy-6-methyl-2-pyridone structure (XII-483) is consistent with its NMR, ir, and uv spectra and is similar to that of 4-hydroxy-2-pyridone. Ultraviolet spectra in water and ethanol and infrared spectra (KBr) show that glutazine and several of its derivatives (XII484 R = H,CN, CONH, C02Et) exist as an equilibrium mixture of the 4-amino-6-hydroxy-2-pyridone (XII-484a) and the 4-aniino-2,6-pyridinedione (XII-484b). ... 

Acetyl-4-hydroxy-6-methyl-2-pyridone and dimethyl sulfate in sodium methoxide give the iV-methyl-2-pyridone (40%) but diazomethane causes 0-methylation (52%). ... 

Chlorination of 4-hydroxy-6-methyl-2-pyridone (MI-660) in water at 40" gives 3-chloro- and 3,5-dichloro-6-methyl-2,4-pyridinediol and 6-chIoromethy 1-3,5-... 

Acetyl-4-hydroxy-6-methyl-2-p5nidone and phosphoryl chloride in acetic acid give 3,5-diacetyl-4 hydro3 -6-methyl-2-pyridone (XII-689). 4-Hydroxy-6-methyl-2-pyridone (XD-690, R = H), l,6-dimethyl-4-hydror -2-pyridone... 

Acetyl-4-hydroxy-6-methyl-2-pyridone oxime, 641 5 -Acetyl-4-hydroxy-6-methyl-2-pyridone, 634 acetylation, 658, 816 N-alkylation with dimethyl sulfate, 765... 

N-arylhydrazones of perchloro-2/4-pentadienal, 604 3 -Aryl-4-hydroxy-6-methyl-2-pyridone, 661... 

Piperidine and pyridine added at room temp, to a stirred soln. of 4-hydroxy-6-methyl-2-pyridone in methanol-ethanol, after 5 min. isovaleraldehyde added drop-wise during 3 min., and refluxed 16 hrs. product. Y 80%. F. e. s. J. A. Findlay et al.. Can. J. Chem. 54, 270 (1976). 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

Dichloro-1,4-naphthoquinone and 3-methyl-l-phenylpyrazolone gave 400, and the tetracyclic quinone 401 was obtained from l,2-dimethyl-4-hydroxy-6-pyridone (47CB47). Cyclization of 6-acetylamino-7-chloroquin-oline-5,8-dione in the presence of acetic anhydride yielded the oxazolo derivative 402, and from the 7-mercapto analog the thiazole quinone 403 was... 

A rapid and simple separation method for Ga and Zn involves extraction of Gam from aqueous acidic solutions by l-phenyl-2-methyl-3-hydroxy-4-pyridone.503... 

Among examples of lactam-lactim tautomerism pyridine derivatives 98a, 98b, and 100 have been proven to be pyridones on the basis of their IR spectra, whereas UV and IR spectra suggest the aminopyridine structure 101 (63BCJ633). Spectral data similarly confirm the existence of substance 31a (Scheme 57) in the 4-hydroxy-2-pyridone form rather than the 2,4-dihydroxypyridine form 234 (74BCJ1750). Consequently, its acetylation by acetic anhydride/pyridine at 130 °C or methylation yield N,0-disubstituted derivatives 235a and 235b, respectively. Acetylation at 100 °C, however, leads to 0,0 -disubstitution (236). 

Furo-2-pyridones. 1,4-Dimethyl -3- cyano -5-propargyl -6- hydroxy -2-pyridone dissolved in coned. H2SO4, and poured on ice after a few min. 5,6- (2-methyl-furano)-l,4-dimethyl-3-cyano-2-pyridone. Y 70%. F. e. s. J. Reisch, Arch. Pharm. 297, 754 (1964) furo[3,2-c]coumarins s. Arch. Pharm. 299, 457 (1966). 

Hydroxy-2-pyridone (XU-516) and a large excess of diazomethane give 6-methoxy-2-pyridone (2%), 6-methoxy-lmethyl-2-pyridone (4%), 2,6-dimeth-oxypyridine (8%), and the 3-( methylhydrazonc) of l-methyl-2,3,6-pyridine-trione (XD-517) (14%). ° 6-Methoxy-2-pyridone and diazomethane give a mixture of O- and yV-methylation products. 6-Hydroxy- l-methyl-2-pyridone gives 6-methoxy-lmethyl-2-pyridone and XD-517. ° ... 

The two diols, 3- and 5-hydroxy-2-pyridone (XII-569, 30H, 5-OH) are converted to the corresponding -methyl-2-pyridones by treatment with excess methyl iodide. ... 

Hydroxy-2-pyridones form 4-acetoxy-2-pyridones readily. 4-Acetoxy-l, 6-di-methyl-2-pyridone and 4-acetoxy-5-acetyl-6-methyl-2-pyridone have been prepared employing acetic anhydride. 4-Acetoxy-6-methyl-l-phenyl-2-pyridone has been formed with phosphoryl chloride and acetic acid. Methyl citrazinate (XI-597) and acetic anhydride give methyl 2,6-diacetoxyisonicotinate. ... 

The preparative nitration of pyridones has been reviewed recently.The nitrations of several 2- and 4-pyridones have been studied kinetically. Pyridones with p < 1.5 are nitrated as their free bases under all conditions. 4-Pyridone (p g 3.27) is nitrated as the free base in 65 to 85% sulfuric acid but as the conjugate acid in 85 to 98% H2S04." 6-Hydroxy-2-pyridone and its N- and 0-methyl derivatives are rapidly converted to the... 

Cyano-6-hydroxy-2-pyridones, by cyclization, 625 3-Cy suio-6-hydroxy-4-tri f luoro-methyl-2-pyridone, 624 3-Cyano-6-hydroxy-4-tri fluoro-methyl-2-pyridone, 625... 

A new ricinine metabolite was conclusively identified as O-demethyl-ricinine (see Figure 6.14) (Lee and Waller, 1972a) (A -methyl-3-cyano-4-hydroxy-2-pyridone), and this interconversion with ricinine in senescent and green castor plant leaves was demonstrated. [3,5- dRicinine adminis-... 

Mocimycin has been chemically converted to aurodox by protection of the 4-hydroxy group at the pyridone moiety as the benzoylformate, followed by /V-methylation and hydrolytic removal of the protective group (1,55). Whereas aurodox esters are active growth promotors in animals, goldinamines that are A/-acylated by acids other than goldinonic acid, such as acetic, benzoic, or arylsulfonic acids, lack useful antimicrobial or growth-promoting activity (1). 

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

The importance of ring size holds also for tautomerism of -pyrrol-5-ones and. d -dihydro-6-pyridones. While the former compounds behave as cyclic 1-methyl-2-alkyl-2-hydroxy-5-pyrrolidones 179) (76) [or, on distillation, as the dehydrated l-methyl-2-alkyl-J -pyrrolones (77)], the latter compounds exist as acyclic N-methylamides of 8-oxo-acids (78) [as shown by infrared spectroscopy (/80)j. The dehydration of 78 during distillation to form l-methyl-2-alkyl-. -dihydro-6-pyridones (79) is achieved only with difficulty. 

Methyl- and 3-phenyl-4-hydroxy-2-oxo-2//-pyrido[2,1 -Z)]oxazinium inner salts were prepared in the reaction of 2-pyridone and 2-substituted malonyl chloride, prepared in situ from 2-substituted malonic acid with PCI5 in CH2CI2 (00JCS(P2)2096). 

Chemical Name 6-Cyclohexy -1-hydroxy-4-methyl-2(1H)-pyridone ethanolamine salt Common Name —... 

Methylquinoline (2) 3-methyl-2(lH)quinolinone (3) 5,6-dihydro-5,6-dihydroxy-3-me thy 1-2(1 H)quinolinone (4) 6-hydroxy-3 -methyl-2( 1 H)quinolinone (5) 5,6-dihydroxy-3-methyl-2(lH)quinolinone (6) 3-methyl-2,4,6-trihydroxypyridine (1) 4-Methylquinoline (2) 4-methyl-2(lH)quinolinone (3) 7,8-dihydro-7,8-dihydroxy-4-methy 1-2(1 H) quinolinone (4) 8-hydroxy-4-methyl-2(lH)quinolinone (5) 7,8-dihydroxy-4-methyl-2(1 H)quinolinone (6) 6-hydroxy-5-(2-carboxyethenyl)-4-methyl-2( 1 H)pyridone... 

The microwave-assisted nucleophilic substitution of 4-hydroxy-6-methyl-2(lH)-pyridones [101] has also been studied (Scheme 8.72). 

Grabowska et al [112] reported methylation of 2-hydroxypyridine with methanol over hydrothermally synthesized zinc aluminate spinels. N-methyl-2-pyridone was formed selectively (95%) and 100% 2-hydroxy pyridine conversion was achieved at 340°C. During the experiment the activity of the catalyst was shown to be stable and catalyst can be regenerated repeatedly without any significant loss of activity by passing air through the catalyst bed at 500°C. 

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