Method for producing maleimide polyethylene glycol derivative

Patent metadata

Field	Value
Publication number	US-12595336-B2
Application number	US-202118256951-A
Country	US
Kind code	B2
Filing date	Dec 8, 2021
Priority date	Dec 15, 2020
Publication date	Apr 7, 2026
Grant date	Apr 7, 2026

Abstract

A method for producing a maleimide polyethylene glycol derivative, may including a reaction step of heating a maleimide polyethylene glycol derivative having a protective group, in a solvent in the presence of silica gel to cause deprotection. A maleimide polyethylene glycol derivative can be produced at a high maleimidization rate while restraining deterioration of a maleimide group on deprotecting the maleimide polyethylene glycol derivative having a protective group.

First claim

The invention claimed is:

1 . A method for producing a maleimide polyethylene glycol derivative represented by the following general formula (2), comprising a reaction step of heating a maleimide polyethylene glycol derivative having a protective group represented by the following general formula (1), in a solvent in the presence of silica gel to cause deprotection:

wherein R 1 , R 2 , R 3 , and R 4 each independently represents a group selected from a hydrogen atom, an alkyl group, a halogen atom, a cyano group, a formyl group, an acyl group, a carboxy group, an acyloxy group, and an alkylcarbonyloxymethyl group,
Z is a residue obtained by removing active hydrogen groups from a compound having 2 to 5 active hydrogen groups,
Y 1 and Y 2 each independently represents a single bond, an ether bond, an amide bond, an ester bond, a urethane bond, a carbonate bond, a thioether bond, a disulfide bond, a thioester bond, or an alkylene group containing any of them,
W is a group selected from an ether group, a methylene group and a dimethylvinylidene group,
X is a hydrocarbon group having 1 to 7 carbon atoms, a protective group for a hydroxy group, a protective group for a carboxy group, a protective group for a thiol, a cyano group, or an alkylene group containing any of them,
m1 and m2 each independently is 1 or 0,
n1 represents the number of repeating units of the polyethylene glycol and is an integer of 0 or 10 to 2000,
n2 represents the number of repeating units of the polyethylene glycol and is an integer of 10 to 2000,
l represents the number of repeating units of the methylene group and is an integer of 0 or 2 to 10,
a is an integer of 1 to 5, b is an integer of 0 to 4, and the sum of a and b is an integer of 2 to 5.

2 . The method of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 in the general formula (1) each independently is a hydrogen atom or an alkyl group.

3 . The method of claim 1 , wherein W in the general formula (1) is an ether group.

4 . The method of claim 1 , wherein, in the general formulae (1) and (2), Z is a residue obtained by removing active hydrogen groups from a compound having 2 active hydrogen groups, m1 and m2 each is 1, n1 and n2 each is an integer of 10 to 2000, l is 2, and a and b each is 1.

5 . The method of claim 1 , wherein, in the general formulae (1) and (2), Z is a residue obtained by removing active hydrogen groups from a compound having 3 active hydrogen groups, m1 is 0, m2 is 1, n1 is 0, n2 is an integer of 10 to 2000, l is 0, a is 1, and b is 2.

6 . The method of claim 1 , wherein, in the general formulae (1) and (2), Z is a residue obtained by removing active hydrogen groups from a compound having 4 active hydrogen groups, m1 is 1, n1 is from 10 to 2000, l is 2, a is 4, and b is 0.

Assignees

• Nof Corp

Inventors

• Ozone Daiki
• Mori Shota
• Ota Masaki

Classifications

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C08G65/33337 Primary

  cyclic · CPC title

• C08G65/33331 Primary

  containing imide group · CPC title