Complexes and Ligands

A method of making a compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein:
• each X1 is independently selected from H, halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3,
• the method comprising deprotecting a compound of Formula (IIa):
• or a salt thereof, wherein each P1 is independently a protecting group,
• to obtain the compound of Formula (II).

A compound of Formula (III):

• or a pharmaceutically acceptable salt thereof, wherein:
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each Y is selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, and a bond;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each m is an integer from 0 to 100;
• wherein if m is 0 then L is a bond;
• and
• each Z is selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter;
• wherein:
• if Y is a bond and m is 0, then Z is H or C1-3 alkyl;
• and
• at least one m is greater than 0.

A method of making a compound of Formula (IIIc):

• or a pharmaceutically acceptable salt thereof, wherein:
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• the method comprising deprotecting a compound of Formula (IIId):
• wherein each P1 is independently a protecting group,
• to obtain the compound of Formula (IIIc).

A method of making a compound of Formula III(f):

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is selected from C1-6 alkylene, C2-6 alkenylene, and C2-6 alkynylene;
• x is an integer from 0 to 100;
• wherein if x is 0 then L is a bond;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• the method comprising deprotecting a compound of Formula (IIIg):
• or a salt thereof, wherein each P1 is independently a protecting group, to obtain the compound of Formula (IIIf).

A method of making a compound of Formula (IIIi):

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is selected from C1-6 alkylene, C2-6 alkenylene, and C2-6 alkynylene;
• x is an integer from 0 to 100;
• wherein if x is 0 then L is a bond;
• y is an integer from 0 to 100, wherein if y is 0 then L is a bond and Z is H or C1-3 alkyl;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each Z is selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter;
• the method comprising coupling a compound of Formula (IIIf):
• or a salt thereof, with a compound of formula (15):
• H2N-(L)y-Z (15),
• or a salt thereof, to obtain the compound of Formula (IIIi).

A compound of Formula (IV):

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, and a bond;
• each L1 is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each L2 is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• x is an integer from 0 to 100;
• wherein if x is 0 then L1 is a bond and Z1 is H or C1-3 alkyl;
• y is an integer from 0 to 100;
• wherein if y is 0 then L2 is a bond and Z2 is H or C1-3 alkyl;
• Z1 and Z2 are each independently selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter.

A method of making a compound of Formula (IVc):

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, and a bond;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each L1 is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each L2 is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each X1 is independently selected from halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• x is an integer from 0 to 100;
• wherein if x is 0 then L1 is a bond and Z1 is H or C1-3 alkyl;
• y is an integer from 0 to 100;
• wherein if y is 0 then L2 is a bond and Z2 is H or C1-3 alkyl;
• n is an integer from 0 to 100, wherein if n is o then L is a bond;
• and
• Z1 and Z2 are each independently selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter;
• the method comprising coupling a compound of Formula (IVd):
• or a salt thereof, with a compound of formula (16):
• H2N-(L1)x-Z1 (16),
• or a salt thereof, to obtain the compound of Formula (IVc).

A compound of Formula (V):

• or a pharmaceutically acceptable salt thereof, wherein:
• X2 is selected from any one of the following groups:
• each X1 is independently selected from H, halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3.

A compound of Formula (VI):

• or a pharmaceutically acceptable salt thereof, wherein:
• X2 is selected from any one of the following groups:
• X3 is selected from CH, C-Hal, and N;
• each X1 is independently selected from H, halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• and
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3.

A compound of Formula (VII):

• or a pharmaceutically acceptable salt thereof, wherein:
• X2 is selected from any one of the following groups:
• each X1 is independently selected from H, halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each Y is selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, and a bond;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each m is an integer from 0 to 100;
• wherein if m is 0 then L is a bond;
• and
• each Z is selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter;
• wherein:
• if Y is a bond and m is 0, then Z is H or C1-3 alkyl;
• and
• at least one m is greater than 0.

A compound of Formula (VIII):

• or a pharmaceutically acceptable salt thereof, wherein:
• X2 is selected from any one of the following groups:
• X3 is selected from CH, C-Hal, and N;
• each X1 is independently selected from H, halo, NO2, CN, N3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each R1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, SH, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, NO2, CN, C(O)OH, C1-3 alkoxy, C1-3 haloalkoxy, and N3;
• each Y is selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, and a bond;
• each L is independently selected from C1-3 alkylene, C2-4 alkenylene, C2-4 alkynylene, C1-3 alkylene-O—, —O—C1-3 alkylene, phenylene, —C(O)NH—, —NHC(O)—, —C(O)O—, and —OC(O)—;
• each m is an integer from 0 to 100;
• wherein if m is 0 then L is a bond;
• and
• each Z is selected from H, C1-3 alkyl, an activated ester, a biorthogonal functional group, NH2, C1-3 alkylamino, di(C1-3 alkyl)amino, a maleimide, a fluorophore, a probe, a fluorescent quencher, a chromophore, a nanoparticle, a quantum dot, biotin, desthiobiotin, a chemical substrate tag, a biomolecule, a dye, a photocrosslinking label, and a quencher that can function as a reporter;
• wherein:
• if Y is a bond and m is 0, then Z is H or C1-3 alkyl;
• and
• at least one m is greater than 0.