US 12,227,522 B2
Synthesis of structural analogs of largazole and associated compounds
Robert M. Williams, Ft. Collins, CO (US); Sivanagireddy Koti, Ft. Collins, CO (US); Subhadip De, Ft. Collins, CO (US); Anil M. Shelke, Ft. Collins, CO (US); Ryan E. Cerbone, Ft. Collins, CO (US); and Nobuyoshi Yasuda, Ft. Collins, CO (US)
Assigned to COLORADO STATE UNIVERSITY RESEARCH FOUNDATION, Fort Collins, CO (US); and CETYA THERAPEUTICS, INC., Fort Collins, CO (US)
Appl. No. 18/255,969
Filed by COLORADO STATE UNIVERSITY RESEARCH FOUNDATION, Fort Collins, CO (US); and CETYA THERAPEUTICS, INC., Fort Collins, CO (US)
PCT Filed Dec. 16, 2021, PCT No. PCT/US2021/063719
§ 371(c)(1), (2) Date Jun. 5, 2023,
PCT Pub. No. WO2022/140144, PCT Pub. Date Jun. 30, 2022.
Claims priority of provisional application 63/128,273, filed on Dec. 21, 2020.
Prior Publication US 2024/0059709 A1, Feb. 22, 2024
Int. Cl. C07D 513/18 (2006.01)
CPC C07D 513/18 (2013.01) 14 Claims
 
1. A method for preparing a compound of formula (III):

OG Complex Work Unit Chemistry
the method comprising:
reacting a compound of formula (I):

OG Complex Work Unit Chemistry
with an activating agent selected from C1-C20 linear or branched alkyl-sulfonyl halide, substituted alkyl-sulfonyl halide, arylsulfonyl halide, substituted arylsulfonyl halide, halo-phosphite, or a halogenating reagent, thereby forming a compound of formula (II):

OG Complex Work Unit Chemistry
and reacting the compound of formula (II) with a nucleophile comprising an R1 group, thereby forming the compound of formula (III);
wherein:
X is O or NH;
Ar is thiazolyl, pyridinyl, or oxazolyl;
R1 is R2COS, R3S, or R4R5N;
R2, R3, R4, and R5 independently are hydrogen, C1-C24 linear alkyl, C1-C24 linear alkyl substituted with one or more aryl or heteroaryl in any position, C1-C24 branched alkyl, C1-C24 branched alkyl substituted with one or more aryl or heteroaryl in any position, C3-C24 cyclic alkyl, C3-C24 cyclic alkyl substituted with one or more aryl or heteroaryl in any position, C2-C24 alkenyl, C2-C24 alkynyl, aryl, heteroaryl, diphenyl methyl, or triphenylmethyl; and
L is a leaving group selected from C1-C24 linear or branched carbon sulfonate, substituted C1-C24 linear or branched sulfonate, arylsulfonate, substituted arylsulfonate, heteroarylsulfonate, substituted heteroarylsulfonate, phosphate, or halogen.