Methods for preparing polymeric reagents and compositions of polymeric reagents

The composition resulting from carrying out the synthetic method comprising:

• (a) combining a composition comprising an aprotic solvent and a hydroxy-terminated, water-soluble polymer having the following structure:
• CH3O—(CH2CH2O)n—CH2CH2—OH
• wherein (n) is an integer from 2 to about 4000, with a composition comprising di(1-benzotriazolyl) carbonate, wherein the composition comprising the di(1-benzotriazolyl) carbonate is added such that there is an excess of the di(1-benzotriazolyl) carbonate relative to the hydroxy-terminated, water-soluble polymer, to thereby result in a composition comprising an active carbonate ester of the water-soluble polymer having the following structure:
• wherein (n) is an integer from 2 to about 4000, and unreacted di(1-benzotriazolyl) carbonate;
• (b) adding a composition comprising a reactive molecule selected from the group consisting of water, a lower alkyl monohydric alcohol, hydrogen sulfide and a lower alkyl monobasic amine to the composition comprising the active carbonate ester of a water-soluble polymer and unreacted di(1-benzotriazolyl) carbonate, wherein the composition comprising the reactive compound is added such that substantially all of the unreacted di(1-benzotriazolyl) carbonate is substantially consumed;
• (c) reacting the active carbonate ester of a water-soluble polymer lysine to form a polymeric lysine derivative;
• (d) reacting the polymeric lysine derivative in one or more reactions to form a polymeric reagent;
• and
• (e) reacting the polymeric reagent with an active agent under conjugation conditions to thereby result in a water-soluble polymer-active agent conjugate.