US 11,078,162 B2 · Processes for preparing AG-10, its intermediates, and salts thereof

Abstract

Provided herein are improved processes for the preparation of a compound of Formula IX (AG-10). Also provided herein are pharmaceutically acceptable salts of Formula I and Formula Ib as well as crystalline types of Formula IX (AG-10). The processes described herein provide improved yields and efficiency, while the pharmaceutically acceptable salts and crystalline forms provide unexpected pharmacokinetic properties. Other features and aspects of the present disclosure will be apparent to a person of skill in the art upon reading the remainder of the specification.

Claims54

Dependent claims

A method for preparing a compound of Formula IX

comprising
(a) contacting a compound of Formula II
with a compound of Formula III
a first base, and a first organic solvent to provide a compound of Formula IV
wherein each R1 is independently a halogen or a sulfonate ester;
(b) contacting the compound of Formula IV with hydrazine and a second organic solvent
to provide a compound of Formula V
(c) contacting the compound of Formula V with a sulfonating agent or halogenating agent to provide a compound of Formula VI
wherein R2 is a halogen or a sulfonate ester;
(d) contacting the compound of Formula VI with a compound of Formula VII
a second base, and a third organic solvent to provide a compound of Formula VIII
wherein R3 is selected from the group consisting of an C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-8 cycloalkyl, C3-12 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally substituted;
and
(e) contacting a compound of Formula VIII with a third base to provide a compound of Formula IX.

11 more elements

Dependencies are inferred from the claim text.

Processes for preparing AG-10, its intermediates, and salts thereof

Life of this patent

Processes for preparing AG-10, its intermediates, and salts thereof

Life of this patent

Abstract

Claims54