Patent ID: 8568705
Filing Date: 2013-10-29
Classification: A61K,C07D,C08G,C08L,Y02P

Abstract:
1. A method of preparing a multiarm polymer, comprising: (a) to a pentaerythritol bearing four hydroxyl groups, attaching a water-soluble and non-peptidic polymer, wherein the water-soluble and non-peptidic polymer is poly(ethylene glycol), to the pentaerythritol at the site of three of the hydroxyl groups; (b) reacting the pentaerythritol, in one or more reaction steps, with one or more functionalizing reagents to effect substitution of a protected carboxylic acid, —Y, to form a mixture comprising (i) unsubstituted pentaerythritol containing no —Y groups; (ii) a monosubstituted pentaerythritol comprising a single —Y group, and (iii) a multisubstituted pentaerythritol comprising at least two —Y groups; (c) hydrolyzing said protected carboxylic acid to thereby form a carboxylic acid; (d) purifying the mixture to separate the monosubstituted pentaerythritol from the unsubstituted and multisubstituted pentaerythritol species, wherein said purifying step comprises wherein the multiarm polymer has the following structure wherein L and L′ are spacers, and m is defined so as to provide a total molecular weight of the water-soluble and non-peptidic polymer portion of the multiarm polymer of from about 2,000 Da to about 40,000 Da.