A practical procedure for the selective N-alkylation of 4-alkoxy-2-pyridones and its use in a sulfone-mediated synthesis of N-methyl-4-methoxy-2-pyridone

Synthesis and Biological Evaluation of Glycosides and Acyclic Nucleosides Derived 2‐Oxonicotinonitriles

“…The acyclic nucleoside mimics, 2‐ONN derivatives 14 , 16 , 18 , and 20 were prepared by the coupling 7 with 2‐bromomethoxyethyl acetate or 4‐bromobutylacetate, respectively. The ratio of N ‐alkylation/ O ‐alkylation was dependent on the reaction conditions, where the treatment of 7 with 2‐bromomethoxyethyl acetate or 4‐bromobutylacetate (Table , entries 4 and 5) in the presence t ‐BuOk, and n ‐Bu 4 NI in DMF gave selectively the N ‐butylacetate derivatives 14 and 18 , respectively, in good isolated yields. Conducting the alkylation reactions using K 2 CO 3 in reflux acetone resulted in the formation of a separable mixture of the O ‐alkylation products 16 and 20 along with the corresponding N ‐alkylation products 14 and 18 .…”

“…In view of that, the 2‐ONN derivatives 7 was glycosylated with three glycosyl bromides under basic conditions (Table ). Conreaux et al have reported that a selective N ‐alkylation over O ‐alkylation of substituted pyridines was attained under t ‐BuOk, n ‐Bu 4 NI in tetrahydrofuran conditions . Treatment of 7 with peracetylated α ‐ D ‐glucopyranosyl bromide, α ‐ D ‐galacopyranosyl bromide, and α ‐ D ‐lactosyl bromides in the presence of t ‐BuOk and n ‐Bu 4 NI in N,N‐ dimethylformamide (DMF) gave after crystallization the corresponding N ‐glucoside derivatives 8 , N ‐galactoside derivatives 10 , and N ‐lactoside derivatives 12 , respectively, in good yields (Table , entries 1, 2, and 3).…”

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

“…N-alkylated pyridones are valuable scaffolds offering biological activity such as immunomodulators, memory-enhancers and anticancer agents [109,110]. A direct approach to achieve N-alkylated pyridones are less explored and those available present limitations such as poor selectivity and yields, expensive catalyst and poor chemoselectivityy [111,112]. Therefore, in search of a straightforward approach to such molecules.…”

N,N-Dimethylformamide (DMF)-Promoted SpecificN-Alkylation of Hydroxyl N-Heterocycles with Organohalides: A Direct and Efficient Method for Synthesis of Pyridone Derivatives

“…In 1995, Curran group [6] reported that addition of catalytic amount LiBr could also improve the N-alkylation selectivity of 2-hydroxyl pyridines with electron-withdrawing groups at the ortho position. Subsequently, CsF, [7] LiI, [8] NaI, [9] TBAX, [10] etc. were all found to be effective promoters to enhance the N-selectivity.…”