Indenoisoquinoline-releasable polymer conjugates

A method of preparing a compound of Formula (III), comprising;

• (a) providing an activated polymer having the structure:
• (b) reacting the activated polymer with a protected indenoisoquinoline having the structure:
• (c) removing the protecting group from the resulting intermediate of step (b) to form the compound of Formula (III):
• wherein
• A is a capping group or
• R is a substantially non-antigenic water-soluble polymer;
• L1 is a bifunctional linking moiety;
• Y1-4 are independently O, S, or NR12;
• R1, R4, R9, R10, and R12, are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, and substituted C1-6 heteroalkyls;
• R2, R3, R5 and R6 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C1-6 alkoxy, phenoxy, C1-8 heteroalkyls, C1-8 heteroalkoxy, substituted C1-6 alkyls, C3-8 cycloalkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, halo-, nitro-, cyano-, carboxy-, C1-6 carboxyalkyls and C1-6 alkyl carbonyls;
• Ar is an aromatic moiety which when included in Formula (II) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heteroaromatic group;
• (r), (s), (t), and (u) are independently zero or one;
• (m) and (p) are independently zero or a positive integer;
• B1 is a leaving group;
• and
• B2 is a protecting group.