US 12,134,721 B2
Complexes and ligands
Ralph Mazitschek, Belmont, MA (US); N. Connor Payne, Cambridge, MA (US); and Alena Kalyakina, Karlsruhe (DE)
Assigned to The General Hospital Corporation, Boston, MA (US)
Appl. No. 17/287,236
Filed by The General Hospital Corporation, Boston, MA (US)
PCT Filed Oct. 22, 2019, PCT No. PCT/US2019/057501
§ 371(c)(1), (2) Date Apr. 21, 2021,
PCT Pub. No. WO2020/086629, PCT Pub. Date Apr. 30, 2020.
Claims priority of provisional application 62/748,965, filed on Oct. 22, 2018.
Prior Publication US 2022/0025254 A1, Jan. 27, 2022
Int. Cl. C09K 11/06 (2006.01); C07D 487/18 (2006.01); C07D 519/00 (2006.01); C07F 5/00 (2006.01); G01N 21/64 (2006.01); G01N 33/58 (2006.01)
CPC C09K 11/06 (2013.01) [C07D 487/18 (2013.01); C07D 519/00 (2013.01); C07F 5/00 (2013.01); G01N 21/6428 (2013.01); G01N 33/582 (2013.01); C09K 2211/182 (2013.01); G01N 2021/6439 (2013.01)] 20 Claims
 
1. A method of making a compound of Formula (II):

OG Complex Work Unit Chemistry
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:
coupling a compound of Formula (IIb):

OG Complex Work Unit Chemistry
or a salt thereof, with a compound of formula (1):

OG Complex Work Unit Chemistry
or a salt thereof, to obtain the compound of Formula (IIa)

OG Complex Work Unit Chemistry
and
deprotecting the compound of Formula (IIa) to obtain the compound of Formula (II).