Process for the cycloaddition of a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne
Inventors
van Delft, Floris Louis • Dommerholt, Frederik Jan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12084448-B2
Publication Date
2024-09-10
Expiration Date
Abstract
A process is provided, comprising reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne, wherein the (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group 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 a substituent(ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group and wherein the (hetero)cycloalkyne is a (hetero)cyclooctyne or a (hetero)cyclononyne according to Formula (1). The invention also relates to the products obtainable by the process according to the invention.
Core Innovation
The invention relates to a process for preparing a product of a 1,3-dipolar cycloaddition reaction by reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne. The (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group bonded to a (hetero)aryl group, and is a (hetero)aryl azide or a (hetero)aryl diazo compound.
The (hetero)aryl group comprises one or more substituents having a positive value for the para-Hammett substituent constant and/or the meta-Hammett substituent constant, and/or is an electron-poor (hetero)aryl group. Electron-poor (hetero)aryl groups include those bearing a positive charge or having a ratio of number of π-electrons present in the (hetero)aromatic ring system to number of protons present in the nuclei of the (hetero)aromatic ring system below 0.167 for a 6-membered ring or below 0.200 for a 5-membered ring.
The (hetero)cycloalkyne is specified as an aliphatic (hetero)cycloalkyne, wherein both sp1 C-atoms of the carbon-carbon triple bond are bonded to an sp3 C-atom. The disclosure further describes structural formula embodiments and attachment contexts, including linker L and payload A substituents and a glycoprotein context through a saccharide moiety of the glycoprotein glycan.
Claims Coverage
The patent contains one independent claim. It covers a 1,3-dipolar cycloaddition process in which the inventive coverage is determined by the identity of the (hetero)aryl 1,3-dipole and the aliphatic (hetero)cycloalkyne, together with electronic and charge-based criteria defining electron-poor (hetero)aryl character.
Reacting a (hetero)aryl 1,3-dipole with a (hetero)cycloalkyne in 1,3-dipolar cycloaddition
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.
(Hetero)aryl 1,3-dipole as azide or diazo with aryl-bound 1,3-dipole functional group
The (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group bonded to a (hetero)aryl group, wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound.
Hammett- and charge-defined (hetero)aryl dipole electron-poverty
The (hetero)aryl group comprises one or more substituents having a positive value for the para-Hammett substituent constant and/or the meta-Hammett substituent constant, and/or is an electron-poor (hetero)aryl group bearing a positive charge and/or having a ratio of π-electrons to protons lower than 0.167 for a 6-membered ring or lower than 0.200 for a 5-membered ring.
Aliphatic (hetero)cycloalkyne defined by sp1-to-sp3 bonding at the cycloalkyne triple bond
The (hetero)cycloalkyne is an aliphatic (hetero)cycloalkyne wherein both sp1 C-atoms of the (hetero)cycloalkyne carbon-carbon triple bond are bonded to an sp3 C-atom.
The independent claim centers on reacting an azide- or diazo-based (hetero)aryl 1,3-dipole with an aliphatic (hetero)cycloalkyne, where the (hetero)aryl dipole is constrained to electron-poor character via positive Hammett substituent constants, positive charge, and/or a π-electron/proton ratio threshold by ring size.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?