Synthesis and neurothropic properties of 1-(2,6-dichlorophenyl)-3-amino(alkoxy)methyleneindolin-2-one

Abstract

The presence of an active methylene unit in position 3 of the oxindole molecule provides for the ability of condensation of various reagents at this site. Previously we have demonstrated that dimethylformamide diethylacetal smoothly reacts with 1-(2,6-dichlorophenyl)indolin-2-one (Ia) and its derivatives with the formation of the corresponding enamines, the latter being the initial reagents for the synthesis of transamination products and condensed indoles [1][2][3]. In this work we have used a series of lactim esters, including Omethylvalerolactims (II, n = 1), O-methylcaptolactims (II, n = 2), orthoformic ester, and N,N-dimetylacetamide (III), as condensing agents.It was found that, in accordance with the commonly accepted notions [4], the amidacetals are much more reactive than the lactim esters and orthoesters. Indeed, the condensation process with amidacetals proceeds readily even at room temperature, while the interaction with lactim esters II requires boiling in the absence of solvent, and the reaction with orthoformic ester is possible on boiling in the presence of acetic anhydride. This order of reactivity is quite understandable since the behavior of amidacetals in the case under consideration is characterized by equilibrium involving ambidentate cations and alkoxy anions: Here, the anion acts as an acceptor of the 3-H proton of the indolinone cycle and the Ilia cation serves an electrophilic agent. The weakly basic lactim esters II are much less