Alkylation of 3-aminoisocarbostyryl derivatives

Abstract

In this work, we continued our study of the chemical properties of uncondensed derivatives of 3-aminoisoquinolin-1(2H)-one (3-aminoisocarbostyryl) [1,2] and examined the reaction of alkyl halides with isocarbostyryls substituted at the 3-amino group. The alkylation of 3-aminoisocarbostyryls has been studied previously predominantly for condensed systems (reactions with alkyl halides [3-6] and dimethyl sulfate [7]). Only the 1,4-conjugate addition of olefins to 3-aminoisoquinolin-1(2H)-one has been described for uncondensed derivatives [8].Electrophilic substitution in 3-aminocarbostyryls, which are ambident nucleophiles, leads to different products depending both on the structure of the reagents and reaction conditions [3][4][5][6][7]. Thus, heating solutions of 3-(arylamino)isoquinolin-1(2H)-ones 1a-c and 3-(alkylamino)isoquinolin-1(2H)-ones 1d and 1e in acetonitrile with phenacyl bromide or alkyl halides (MeI, EtI, benzyl chloride) leads to a complex mixture of reaction products, which failed to be separated. The same result was obtained in an attempt to carry out the reaction by fusion of a mixture of reagents (with phenacyl bromide and benzyl chloride) or heating of the mixture in the presence of i-OPrNa in 2-propanol (according to mass-spectrometric and 1 H NMR spectral data).We have found that compounds 1a,b,d,e react with alkyl halides (MeI, EtI, and benzyl chloride) in DMF solution at room temperature in the presence of NaH and are converted into 3-(alkylanilino)isoquinolin-1(2H)-ones 2a and 2b and 3-(dialkylamino)isoquinolin-1(2H)-ones 2c-e.Isoquinolinones 2a-e were isolated from the reaction product mixtures as pure compounds and their structures were established using 1 H NMR spectroscopy (Tables 1-3).

Synthesis of fused pyrimidine derivatives using NCNCC+C approach

“…Авторами роботи [26] була детально досліджена взаємодія 3-(ариламіно)-та 3-(гетариламіно) ізохінолін-1(2Н)-онів з ароматичними альдегідами. Було знайдено, що при використанні ариламіноізохінолінонів похідні піримідину не утворюються.…”