Improved Synthesis and Reaction of 11‐Chloroneocryptolepines, Strategic Scaffold for Antimalaria Agent, and Their 6‐Methyl Congener from Indole‐3‐carboxylate. (30th January 2014)

• Record Type: Journal Article
• Authors: Wang, Li; Lu, Wen‐Jie; Odawara, Tomohito; Misumi, Ryuhei; Mei, Zhen‐Wu; Peng, Wei; El‐Sayed, Ibrahim El‐Tantawy; Inokuchi, Tsutomu
• Is Part Of: Journal of heterocyclic chemistry. Volume 51:Number 4(2014)
• Page Start: 1106
• Page End: 1114
• Publication Date: 2014-01-30
• Subjects: Heterocyclic compounds -- Periodicals; 547.59
• DOI: 10.1002/jhet.1617
• Languages: English
• ISSNs: 0022-152X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Various 11‐chloro‐5‐methyl‐5<italic>H</italic>‐indolo[2, 3‐<italic>b</italic>]quinolines (neocryptolepines) with different substituents on the quinoline ring, key intermediates for antimalaria agents, are prepared from the substituted <italic>N</italic>‐methylanilines, easily accessible by the <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink"><italic>N</italic>‐methylation</named-content> of anilines, and indole‐3‐carboxylate as a counterpart. This protocol is benign in terms of the reduced number of steps to reach the target, compared with the known method using anilines, and easy <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">product purification</named-content>. Alternatively, their 6‐methyl congener is prepared by <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink"><italic>N</italic>‐methylation</named-content> of the indole moiety of 2‐arylaminoindole‐3‐carboxylate followed by successive <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">cyclization</named-content> and <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">chlorination</named-content>. 11‐Chloroneocryptolepines are found more reactive than their 6‐methyl congener in the <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">nucleophilic substitution</named-content> at the C11 position.</p> </abstract>