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1. (WO2018158592) PROCESS FOR THE PRODUCTION OF TETRAAMINOBIPHENOL MACROCYCLIC LIGANDS; AND NOVEL TETRAAMINOBIPHENOL MACROCYCLIC LIGANDS

Pub. No.:    WO/2018/158592    International Application No.:    PCT/GB2018/050547
Publication Date: Sat Sep 08 01:59:59 CEST 2018 International Filing Date: Sat Mar 03 00:59:59 CET 2018
IPC: C07D 257/10
C07D 487/06
Applicants: ECONIC TECHNOLOGIES LTD
Inventors: KEMBER, Michael
CHARTOIRE, Anthony
BLACKBURN, Anthea
DRANE, Samuel
Title: PROCESS FOR THE PRODUCTION OF TETRAAMINOBIPHENOL MACROCYCLIC LIGANDS; AND NOVEL TETRAAMINOBIPHENOL MACROCYCLIC LIGANDS
Abstract:
A process for preparing a tetra-substituted aminobiphenol macrocyclic ligand having the structure (I), comprising the step of treating a precursor compound having the structure (II) with a compound having the structure R6-L where L represents a leaving group (hereinafter compound (III)) in the presence of a base; wherein R1 and R2 are independently selected from hydrogen, halide, a nitro group, a nitrile group, an imine group, -NCR13R14, an amine, an ether group -OR15 or -R16OR17, an ester group -OC(O)R10 or - C(O)OR10, an amido group -NR9C(0)R9 or -C(0)-NR9(R9), -COOH, -C(0)R15, -OP(0)(OR18)(OR19),- P(O)R20R21, a silyl group, a silyl ether group, a sulfoxide group, a sulfonyl group, a sulfinate group or an acetylide group or an optionally substituted alkyl, alkenyl, alkynyl, haloalkyl, aryl, heteroaryl, alkoxy, aryloxy, alkylthio, arylthio, alicyclic or heteroalicyclic group; R3 is independently selected from optionally substituted alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene, arylene, heteroarylene or cycloalkylene, wherein alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene and heteroalkynylene, in each case optionally interrupted by aryl, heteroaryl, alicyclic or heteroalicyclic; R4 is independently selected from hydrogen, or optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl; R5 is independently selected from hydrogen, optionally substituted aliphatic, heteroaliphatic, alicyclic, alkanoate, arylate, carboxyl, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl, or two R5 species may together be selected from optionally substituted alkylene, alkenylene or alkynylene, bonded to two different N groups of the compound of structure (II), with the proviso that at least one of the species R5 is hydrogen; and E is independently selected from NR5 and NR6, with the proviso that at least one of the species E is NR6; wherein R6 is independently selected from optionally substituted aliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, ether, polyether, or optionally substituted alkylaryl or alkylheteroaryl; wherein R9, R10, R13, R14, R18, R19, R20 and R21 are independently selected from hydrogen or an optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl group and R15, R16 and R17 are independently selected from an optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl group; and wherein the molar ratio of compound (III) to the number of NH sites in the compound of structure (II) is at least 0.6. In embodiments of the invention the molar ratio of compound (III) to species R5 which are hydrogen in compound (II) is at least 1. Surprisingly, it has been determined that N-alkylation of the compound of structure (II) takes place efficiently despite the presence of phenol groups would be expected to be sites for O-alkylation. Also described are certain novel ligands having asymmetrical R5 and R6 groups.