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US 8,193,306 B2Granted
Methods for preparing polymeric reagents and compositions of polymeric reagents
AssigneeNektar Therapeutics
InventorsAntoni Kozlowski, Jon McKannan, Samuel P. McManus
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Abstract
Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.
Claims4
A 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 sulfate 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;
- and
- (c) reacting the active carbonate ester of a water-soluble polymer lysine to form a polymeric lysine derivative.
4 more elements
Dependencies are inferred from the claim text.