Patent EP-3589621-A1 (EP)
Inventor: KEMBER MICHAEL
IPC: C07D487/06
Filed: 2018-03-02
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 R 6 -L where L represents a leaving group (hereinafter compound (III)) in the presence of a base; wherein R 1  and R2 are independently selected from hydrogen, halide, a nitro group, a nitrile group, an imine group, -NCR 13 R 14 , an amine, an ether group -OR 1 
 5  or -R 16 OR 17 , an ester group -OC(O)R 10  or - C(O)OR 10 , an amido group -NR 9 C(0)R 9  or -C(0)-NR 9 (R 9 ), -COOH, -C(0)R 15 , -OP(0)(OR 18 )(OR 19 ),- P(O)R 2 
 0 R 21 , 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; R 3  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; R 4  is independently selected from hydrogen, or optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl; R 5  is independently selected from hydrogen, optionally substituted aliphatic, heteroaliphatic, alicyclic, alkanoate, arylate, carboxyl, heteroalicyclic, aryl, heteroaryl, alkylheteroaryl or alkylaryl, or two R 5  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 R 5  is hydrogen; and E is independently selected from NR 5  and NR 6 , with the proviso that at least one of the species E is NR 6 ; wherein R 6  is independently selected from optionally substituted aliphatic, alicyclic, heteroalicyclic, aryl, heteroaryl, ether, polyether, or optionally substituted alkylaryl or alkylheteroaryl; wherein R 9 , R 10 , R 13 , R 14 , R 18 , R 1 9, R 20  and R 21  are independently selected from hydrogen or an optionally substituted aliphatic, heteroaliphatic, alicyclic, heteroalicyclic, aryl or heteroaryl group and R 15 , R 16  and R 17  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 R 5  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 R 5  and R 6  groups.