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Synthesis of 3‐Substituted 2‐Indolinones by a Multicomponent Coupling Isocyanide‐Dependent Microwave‐Assisted Intramolecular Transamidation Process
Author(s) -
Maddirala Amarendar Reddy,
Andreana Peter R.
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201501273
Subject(s) - chemistry , intramolecular force , isocyanide , bifunctional , molecule , aryl , amine gas treating , combinatorial chemistry , alkyl , medicinal chemistry , organic chemistry , catalysis
A small‐molecule library synthesis of 3‐substituted 2‐indolinones using methyl isocyanide and a microwave‐assisted intramolecular transamidation process with 10 % TFA in dichloroethane has been achieved in 3 steps. A modified Fe 0 Bechamp‐type reduction of a substituted bifunctional substrate, o ‐nitrobenzaldehyde, renders 3‐substituted 2‐indolinones in yields ranging from 76–91 % (21 examples). Furthermore, it has been determined that symmetrical 2 o N ‐alkyl or aryl substituents, as a component of the amine starting material, suppresses 3‐substituted 2‐indolinone rotameric mixtures and allows for facile compound 1 H NMR characterization. In the absence of methyl isocyanide, 3,4‐dihydroquinazolines or transamidation products predominate under both Brønsted or Lewis acid conditions in reasonable yields.