Pyridine Derivatives. I. 3-Cyano-4-ethoxymethyl-6-methyl-2-pyridone and Some Related Transformation Products

Bruce, William F.; Coover, H. W.

doi:10.1021/ja01240a026

Cited by 28 publications

(12 citation statements)

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“…All the unknowns in the different product mixtures were identified by comparison with authentic samples. [43] and its identity was confirmed by NMR and IR. Methyl ethoxyacetate (7) was prepared by esterification of ethoxyacetic acid with MeOH in the presence of H2S04, b.p.…”

Section: Experimental Partmentioning

confidence: 82%

Reactions of Alkenediazonium Salts. Part 1. 2,2‐Diethoxyethene‐diazonium hexachloroantimonate: A diazonium, a carbenium or an oxonium salt?

Szele¹,

Tencer²,

Zollinger³

1983

Helvetica Chimica Acta

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SummaryReactions of the title compound 1 with various nucleophiles have been studied. The salt behaves like an alkylating agent towards ethers, alcohols and water forming ethyl diazoacetate (2), which reacts further with excess of the nucleophile. A solvent cage mechanism accounting for the observed products is proposed. Thermal decomposition in inert solvents leads to the alkylation of the counter-ion, i.e. formation of chloroethane, and in anisole, alkylation and chlorination of the solvent are also observed.With a standard coupling component, 2-naphtholate ion, no azo coupling reaction of 1 is observed, but instead 14-methyl-14H-dibenzo [a,j]xanthene (17) is formed. The products of the reaction with diethylamine are diethylcyanoformamide (18) and ethyl diethylcarbamate (19). None of the chemistry of salt 1 is explained by the intervention of vinyl cations expected to be formed in a heterolytic dediazoniation. The predominant pathways seem to involve reactions of an oxonium salt (alkylating properties) or, in the case of diethylamine, a carbenium salt (primary nucleophilic attack on the p-C-atom of 1).The free energy barrier to C=C rotation in 1 is estimated to be 75 to 77 kJ/mol (18.0 to 18.5 kcal/mol), a value which falls between those expected for a double and a single bond.Introduction. -In the context of our investigations on the dediazoniation mechanism of aromatic diazonium ions'), comparisons with the reactivity of vinyldiazonium ions are interesting. Owing to their electronic similarity vinyldiazonium ions might be reagents for the formation of vinyl cations.The unsubstituted vinyldiazonium ion, H,C=CH-N,+, is not yet known. Therefore a theoretical study on the vinyldiazonium ion in the gas phase and in aqueous solution is a worthwhile undertaking. With others, we recently made such a study [2] for the gas phase by ab initio (STO-3G and 4-31G), and for solution by CND0/2 methods. This investigation is a continuation of previous theoretical

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Section: Experimental Partmentioning

confidence: 82%

Reactions of Alkenediazonium Salts. Part 1. 2,2‐Diethoxyethene‐diazonium hexachloroantimonate: A diazonium, a carbenium or an oxonium salt?

Szele¹,

Tencer²,

Zollinger³

1983

Helvetica Chimica Acta

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“…Prepared from guanidine bis(trifluoroacetate) salt 80a and 1-methoxy-2,4-pentanedione 33 (46d) (general procedure J) and purified by flash column chromatography (1 f 2% MeOH/ CHCl3) to give compound 81a (77%) as a yellow oil. 1 (R)-2-(4-Benzyl-2-methyl-piperazin-1-yl)-4-methoxymethyl-6-methyl-pyrimidine (81b).…”

Section: General Procedures M Preparation Of Compounds 76a-h By React...mentioning

confidence: 99%

Orally-Effective, Long-Acting Sorbitol Dehydrogenase Inhibitors: Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Novel Heterocycle-Substituted Piperazino-Pyrimidines

et al. 2001

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Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED(90) < or = 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED(90) values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.

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“…3-Amino-4-arylsulfonylpyrazoles 1 and 5 reacted with the sodium salt of 1-methoxy-2,4-pentanedione 16 45 in AcOH at 100°C (Scheme 7) similar to the reaction described above in Scheme 4. These reactions have also yielded approximately equimolar mixtures of, respectively, 46 and 48 or 47 and 49.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and SAR of 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines as potent serotonin 5-HT6 receptor antagonists

Ivachtchenko

Golovina

Кадиева

et al. 2011

Bioorganic & Medicinal Chemistry

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Pyridine Derivatives. I. 3-Cyano-4-ethoxymethyl-6-methyl-2-pyridone and Some Related Transformation Products

Cited by 28 publications

References 0 publications

Reactions of Alkenediazonium Salts. Part 1. 2,2‐Diethoxyethene‐diazonium hexachloroantimonate: A diazonium, a carbenium or an oxonium salt?

Reactions of Alkenediazonium Salts. Part 1. 2,2‐Diethoxyethene‐diazonium hexachloroantimonate: A diazonium, a carbenium or an oxonium salt?

Orally-Effective, Long-Acting Sorbitol Dehydrogenase Inhibitors: Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Novel Heterocycle-Substituted Piperazino-Pyrimidines

Synthesis and SAR of 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines as potent serotonin 5-HT6 receptor antagonists

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