US 12,252,511 B2
Process for the preparation of cyclic depsipeptides
Anthony D. Piscopio, Boulder, CO (US); Xiaoyong Fu, Shanghai (CN); Feng Shi, Shanghai (CN); Huayan Liu, Shanghai (CN); and Zhifeng Li, Shanghai (CN)
Assigned to OnKure, Inc., Boulder, CO (US)
Filed by OnKure, Inc., Boulder, CO (US)
Filed on Jul. 14, 2023, as Appl. No. 18/222,170.
Application 18/222,170 is a continuation of application No. 17/340,731, filed on Jun. 7, 2021, granted, now 11,739,123.
Application 17/340,731 is a continuation of application No. 16/781,233, filed on Feb. 4, 2020, granted, now 11,053,284, issued on Jul. 6, 2021.
Application 16/781,233 is a continuation of application No. 16/127,399, filed on Sep. 11, 2018, granted, now 10,689,419, issued on Jun. 23, 2020.
Application 16/127,399 is a continuation of application No. 15/313,800, granted, now 10,100,089, issued on Oct. 16, 2018, previously published as PCT/US2015/032590, filed on May 27, 2015.
Prior Publication US 2024/0116989 A1, Apr. 11, 2024
Int. Cl. C07K 1/113 (2006.01); A61K 38/15 (2006.01); C07D 498/06 (2006.01); C07D 513/06 (2006.01); C07D 513/14 (2006.01); C07K 1/107 (2006.01); C07K 5/097 (2006.01); C07K 11/00 (2006.01); C07K 11/02 (2006.01)
CPC C07K 11/02 (2013.01) [A61K 38/15 (2013.01); C07D 498/06 (2013.01); C07D 513/06 (2013.01); C07D 513/14 (2013.01); C07K 1/1077 (2013.01); C07K 1/113 (2013.01); C07K 5/0821 (2013.01); C07K 11/00 (2013.01)] 6 Claims
 
1. A method of preparing a thiol of Formula (XXII)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
R1 and R2 are H;
R3 and R4 are independently C1-C10 alkyl;
R5 is H and R6 is C1-C10 alkyl, or R5 is C1-C10 alkyl and R6 is H; and
R12 is H,
the method comprising treating the carbamate of Formula (XVI)

OG Complex Work Unit Chemistry
wherein:
R18 is —CH2CH2Si(CH3)3, (9H-fluoren-9-yl)methyl or tert-butyl;
R19 is —CH2CH2Si(CH3)3 or tert-butyl;
under acidic conditions to provide the amine of Formula (XVII)

OG Complex Work Unit Chemistry
followed by reaction of the compound of Formula (XVII) with the compound of Formula (VII)

OG Complex Work Unit Chemistry
to provide the carbamate of Formula (XVIII)

OG Complex Work Unit Chemistry
followed by treatment of (XVIII) under acidic conditions to provide the amine of Formula (XIX)

OG Complex Work Unit Chemistry
followed by cyclization of (XIX) to provide (XX)

OG Complex Work Unit Chemistry
followed by treatment of (XX) with R12-SH to provide the thiol (XXII).