	US 12,084,448 B2
	Process for the cycloaddition of a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne
Floris Louis Van Delft, Nijmegen (NL); and Frederik Jan Dommerholt, Beuningen (NL)
Assigned to Synaffix B.V., Oss (NL)
Filed by SynAffix B.V., Oss (NL)
Filed on Oct. 15, 2021, as Appl. No. 17/503,138.
Application 17/503,138 is a continuation of application No. 15/113,730, granted, now 11,168,085, previously published as PCT/NL2015/050045, filed on Jan. 26, 2015.
Claims priority of application No. 14152420 (EP), filed on Jan. 24, 2014.
Prior Publication US 2022/0048920 A1, Feb. 17, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61K 47/68 (2017.01); C07C 269/06 (2006.01); C07C 271/18 (2006.01); C07D 225/02 (2006.01); C07D 225/08 (2006.01); C07D 231/54 (2006.01); C07D 249/16 (2006.01); C07D 261/20 (2006.01); C07H 19/10 (2006.01); C07K 14/47 (2006.01)

CPC C07D 487/04 (2013.01) [A61K 47/545 (2017.08); A61K 47/60 (2017.08); A61K 47/6855 (2017.08); C07C 269/06 (2013.01); C07C 271/18 (2013.01); C07D 225/02 (2013.01); C07D 225/08 (2013.01); C07D 231/54 (2013.01); C07D 249/16 (2013.01); C07D 261/20 (2013.01); C07H 19/10 (2013.01); C07K 14/473 (2013.01); C07C 2602/22 (2017.05); C07C 2603/50 (2017.05)]

18 Claims

1. A process for preparing a product of a 1,3-dipolar cycloaddition reaction comprising reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne,

wherein:

the (hetero)aryl 1,3-dipole compound is defined as a compound comprising a 1,3-dipole functional group, wherein the 1,3-dipole functional group is bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound;

wherein:

(i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises one or more substituents having a positive value for the para-Hammett substituent constant op and/or the meta-Hammett substituent constant om, and/or

(ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group, wherein an electron-poor (hetero)aryl group is:

(ii-a) a (hetero)aryl group wherein the (hetero)aromatic ring system is bearing a positive charge, and/or

(ii-b) a (hetero)aryl group wherein the ratio {number of π-electrons present in the (hetero)aromatic ring system}: {number of protons present in the nuclei of the (hetero)aromatic ring system} is lower than 0.167 for a 6-membered ring, or lower than 0.200 for a 5-membered ring;

the (hetero)cycloalkyne is an aliphatic (hetero)cycloalkyne, wherein an aliphatic (hetero)cycloalkyne is defined as a (hetero)cycloalkyne wherein both sp¹C-atoms of the (hetero)cycloalkyne carbon-carbon triple bond are bonded to an sp³C-atom.