Methods for preparing polymeric reagents

A method for preparing a polymeric reagent, comprising

• (a) providing an aromatic moiety bearing a hydroxy group, a first amino group and a second amino group and having the following structure,
• (b) protecting the first amino group and second amino group;
• (c) reacting a functional group reagent with the hydroxy group to result in a hydroxy group bearing a functional group capable of reacting with an amino group of an active agent and resulting in a hydrolyzable carbamate;
• (d) deprotecting the first amino group and second amino group;
• and
• (e) reacting a plurality of poly(alkylene glycol) water-soluble polymers bearing a reactive group with the first amino group and second amino group to result in (i) a first amino group bearing a water-soluble polymer through a spacer moiety, and (ii) a second amino group bearing a second water-soluble polymer through a spacer moiety,
• wherein the polymeric reagent has the following structure:
• and
• POLY1 is a first poly(alkylene glycol),
• POLY2 is a second poly(alkylene glycol):
• X1 is a first spacer moiety;
• and
• X2 is a second spacer moiety.