Functionalized polymers

A method of making a compound comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to a structure of formula (1):

• or a salt thereof,
• wherein:
• A is the point of covalent bonding to the terminus of the polymer backbone;
• E is O;
• K is selected from the group consisting of:
• alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;
• G is selected from the group consisting of:
• hydrogen, alkoxy, and a hydrophobic separation handle;
• Z1 is O;
• Z2 is O;
• L is selected from the group consisting of:
• a divalent radical of a nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;
• M is a protected group that when deprotected is reactive with a biologically active molecule, a group reactive with a biologically active molecule;
• R is absent or selected from the group consisting of:
• hydrogen, a protecting group, a hydrophobic separation handle, or an activating group;
• R1 is absent or a hydrophobic separation handle;
• wherein when M is a protected group that when deprotected is reactive with a biologically active molecule, then R is a protecting group or a hydrophobic separation handle;
• wherein when M is a group reactive with a biologically active molecule, R is absent, hydrogen, or an activating group;
• and
• wherein only one of R, R1, and G can be a hydrophobic separation handle,
• said method comprising:
• a) contacting a water-soluble, non-peptidic, and non-nucleotidic polymer, in a water-free solvent, with a reagent of formula (4):
• wherein:
• R5 and R6 independently from each other represent C1-C6-alkyl or R5 and R6 jointly form a 5- or 6-membered ring with the N to which they are bonded;
• and
• K, G, Z1, Z2, L, M, R, and R1 are as defined for formula (1);
• b) adding an activating reagent;
• and
• c) adding an oxidizing reagent, wherein the P is oxidized from P+3 to P+5,
• to obtain the compound comprising the water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to the structure of formula (1).