Preparation of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction

• Published in: Tetrahedron Vol. 67; no. 49; pp. 9509 - 9517
• Main Authors: Ikuma, Yohei, Nakahira, Hiroyuki
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 09.12.2011
• Subjects: Carbonates; Chemical reactions; Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Inhibitors; Noncondensed benzenic compounds; Optimization; Organic chemistry; Peptidases; Physical Sciences; Preparations and properties; Science & Technology; Silver; Synthesis (chemistry); Tetrahedrons; SYSTEM; DIPEPTIDYL-PEPTIDASE-IV; NUCLEOSIDES; Silver carbonate; High reaction temperature; NUCLEOTIDES; GLUCAGON-LIKE PEPTIDE-1; Palladium-assisted internal biaryl coupling reaction; INHIBITORS; DERIVATIVES; 2-Aminosubstituted-3H-imidazo[4,5-c]quinolin-4(5H)-ones; CYCLIZATION; ALKALOIDS; reaction; Nitrogen heterocycle; Quinoline derivatives; Transition metal; Silver Carbonates; Palladium; 2-Aminosubstituted-3H-imidazo[4,5-c]; Palladium-assisted internal biaryl coupling; High temperature; Imidazoquinoline derivatives; Biological activity; Optimization; Chemical coupling; quinolin-4(5H)-ones; Dipeptidyl-peptidase IV inhibitor; Aromatic compound; Chemical synthesis; Platinoid
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.10.015

Representatives of the 3H-imidazo[4,5-c]quinolin-4(5H)-ones have shown interesting biological activity. We have found 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-one as a potent dipeptidyl peptidase 4 inhibitor. However effective synthesis of this nucleus with various substituents at the 6-9-positions has not been reported. We report herein the development of a novel and efficient synthesis of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction. Our optimization of the reaction conditions revealed that the most important factors for this reaction are use of silver carbonate as a base and high reaction temperature. (C) 2011 Elsevier Ltd. All rights reserved.