L- pyridinone

Trifluoroacetonitrile is activated toward reaction with active methylene groups. Cyclocondensation with dialkyl 3-oxopentanedioates and 1,3-diphenylacetone gave 2,4-dialkoxy-6-(trifluoromethyl)-3,5-pyridinedi-carboxylates (90JOC2964) and 2-(trifluoromethyl)-4(l//)-pyridinones (90JOC380), respectively. 

Job plots have established the stoichiometry of several iron(III)-3-hydroxy-2-methyl-4(l//)-pyridinone systems in aqueous solution.Stability constants have been determined for 1,2-dimethyl-, 1,2-diethyl-, and several other 3-hydroxy-4-pyridinonato-iron(III) complexes. " These data supplement and update the long-standing set of log / 3 values for... 

An alternative method for the synthesis of amrinone from 3-cyano-5-(4-piridyl)-2(l//)-pyridinone (17.2.2) is based on it s acidic hydrolysis to the corresponding acid, 3-carboxy-5-(4-piridyl)-2(l//)-pyridinone (17.2.5), nitration of which with nitrous acid in the presence of sulfuric acid forms 3-nitro-5-(4-piridyl)-2(l//)-pyridinone (17.2.6). Reducing the nitro group of this product with hydrogen gives the desired amrinone (17.2.4) [19, 20]. 

Cyano-5-(4-piridyl)-2(l//)-pyridinone (17.2.2) is also synthesized by condensing 2-(4-piridyl)malonaldehyde with cyanoacetamide [21]. 

Our interest in expanding the acylative pyrrole annulation approach to additional heterocyclic systems has led to an efficient synthesis of pyrrolo[3,2-c]pyridin-2-ones and pyrido[3,4-6]pyrrolizidin-l-ones starting from 4-chloro-N-benzyl-2(l//)-pyridinone and amino acid salts.811 Over the years pyrrolo[3,2-c]pyridines (5-azaindoles)41 have been of interest for applications as elements in new drug design, nucleotide analogues,42 and biochemical tools. However, available synthetic routes to multifunctionalized members from this class of heterocyclic structures are limited.41 43... 

Pyridinamine (54) with diethyl ethoxymethylenemalonate gave ethyl 4-oxo-l,4-dihydro-l,5-naphthyridine-3-carboxylate (55) (reactants, Dowtherm A, 150°C, reflux, 1 h 80%) 101 somewhat similarly, 5-amino-2(l//)-pyridinone gave ethyl 4,6-dioxo-l,4,5,6-tetrahydro-l,5-naphthyridine-3-carboxylate (56) [Et0CH=C(C02Et)2, Ph20, reflux, 1 h 20%].233... 

Amino-6-hydroxy-2(l//)-pyridinone (113) with l-benoyl-2-dimethylami-noethylene gave 4-phenyl-1,6-naphthyridine-5,7(l//,6//)-dione (114) (reactants, AcOH, reflux, 5 min 95%) 757 analogs likewise.469,757,1310... 

RN 29342-05-0 MF Cl2H17N02 MW 207.27 E1NECS 249-577-2 CN 6-cyclohexyl-1-hydroxy-4-methyl-2(l//)-pyridinone... 

Azine approach. It is claimed that a stepwise procedure is required for the preparation of oxazolo[5,4-6]pyridines (246) from 3-amino-2(l//)-pyridinones firstly the amino group... 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

Deuterium and C labeling studies demonstrate that ylide 1021 rapidly rearranges to the A -methyl-2-dehydro-pyridinium ylide 1028, by an intermolecular mechanism (Scheme 201) <1997JA5091>. Ylide 1028 can be trapped with added acids or with O2 to form l-methyl-2(l//)-pyridinone 1030 via stabilized carbonyl oxide 1029. 

The aza-Diels-Alder reaction of substituted lf/-indole-2-carbaldehydes 1323 with Danishevsky s diene 1324 proceeds with a high degree of diastereoselectivity providing highly functionalized l-R -2-(Tmethyl-lf/-indol-2-yl)-2,3-dihydro-4(l//)-pyridinones 1325 which were further elaborated into novel polycyclic heterocycles (Equation 289) <2002TL29>. Attempts to form the imine of 12/-indole-2-carbaldehyde 1326 in situ in the presence of diene 1324 and zinc chloride or zinc triflate at 0 °C or at room temperature did not afford the expected cycloadduct 1327. Instead, 2-(177-indol-2-yl)-2,3-dihydro-477-pyran-4-one 1328 and the 5-hydroxy-l-methoxy-5-(l/7-indol-2-yl)-Tpenten-3-one 1329 were isolated in 45% and 25% yields, respectively (Equation 290). 

In contrast to the unreactive 2-(l//)-pyridinone (27), the much more reactive 4-hydroxy-2-( H )-pyridinone (31) (cf. 7 and 8 in Section III,A) is easily aminated by boiling it in excess benzylamine to give 32 in 89% yield (84S765). Some heterocycles, such as methyl-4-oxo-l, 4-dihydroquinoline-2-carboxylate (33), are transformed by ihe very reactive chlorosulfonyl-isocyanate (CSl) or other reactive sulfonyl- or acylisocyanates in acetonitrile of 1,2-dichloroethane at room temperature with evolution of carbon dioxide to intermediates such as 34, which are hydrolyzed by aqueous hydrochloric acid to methyl-4-aminoquinoline-2-carboxylate (35)... 

On reaction with amines R NHR, only the AE (reaction sequence A) with C—O bond scission will lead to amination product 37 and sulfonic acid 38, whereas the competing attack on the sulfonyl group (reaction sequence B) with S—O bond scission will lead to 2-(l//)-pyridinone (27) and a sulfonamide 39, thus decreasing the yield of the desired amination product (cf. 209 210 in Section IV,E). This B-type of scission is also... 

In this chapter we ntilise the generally accepted terms 2-pyridone , 4-pyridone rather than the strictly correct 2(l//)-pyridinone , etc. 

Azine approach. Oxazolo[3,2-a]pyridinium salts (210) were first obtained from the cyclodehydration reaction of l-phenacyl-2(l//)-pyridinone in sulfuric acid (67JHC66). These salts can also be prepared from 2-halo-1-phenacylpyridinium derivatives (211) by treatment with a base which causes ylide formation and hence cyclization by intramolecular substitution (69JOC2129, 76CB3646). It is recommended that a bulky tertiary amine is used as base in order to avoid opening of the ring or substitution of the 2-halo substituent in the starting material (211). Isoquinoline and quinoline analogues have also been prepared by these methods. 

The thermal stability of hydroxy-N-heterocycles, which usually exist in the lactam form (Sections II—IV), has the consequence that the elimination of water during amination occurs only under forcing reaction conditions. In the absence of acidic catalysts, 2-(l//)-pyridinone (27) is aminated by ammonia, upon heating for 3z hr at 350°C and 100 bar, to give 2-amino-pyridine (28). The analogous amination of 27 with the weakly basic aniline furnishes, after 5 hr at 350°C, only 30% of 2-phenylamino-pyridine (29), whereas reaction of 27 with 2-aminopyridine gives rise to 20-30% 2,2 -dipyridylamine (30) (7IGEP2032403). 

Whereas 2-tosyloxypyridine does not react with dimethyl- or diethyla-mine even under vigorous conditions, 2-methanesulfonyloxypyridine undergoes only S—O bond scission to give 2-(l//)-pyridinone and N,N-dimethylmethanesulfonamide [79JCR(S)I25], 5-Chloro-2-( H )-pyridinone... 

Catalytic amounts of amine salts such as dimethylamine hydrochloride or POCl3 seem to improve the yields (70IZV953 72JHC1235). HMPA converts 4-(l//)-pyridinone (40) in 57% yield to the nucleophilic catalyst DMAP (228) and converts 2-( 1H )-pyridinone (27) in 44% yield to 2-dimethylaminopyridine (229) (73S301). 

The bifunctional ligand 3-cyano-6-methyl-2(l//)-pyridinone (HL53) as shown in Fig. 33, possesses both a coordination group (CN) and a... 

Hydroxy-3-inethylpentanoic acid - 3-Hydroxy-2-methyl-4(l -pyridinone... H-80210 - H-80214... 

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