Process for preparing 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid
Inventors
Gorin, Boris I. • Lanthier, Christopher M. • Luong, Anne Buu Chau • Copp, James Densmore • Gonzalez, Javier
Assignees
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Publication Number
US-11713298-B2
Publication Date
2023-08-01
Expiration Date
Abstract
Disclosed herein are methods and processes of preparing vadadustat and pharmaceutically acceptable salts thereof, and intermediates of formula (I) and their salts useful for the synthesis of vadadustat.
Core Innovation
The invention relates to an improved process for preparing a compound of Formula (8) or a salt thereof, framed for vadadustat and pharmaceutically acceptable salts. The process includes contacting a compound of Formula (I) or a salt thereof with a hydrolyzing agent to reach the compound of Formula (8) or a salt, and the described scope includes broad substitution in Formula (I) and product and intermediate purity/composition requirements.
The compound of Formula (I) or a salt thereof is prepared by step a), step b), and then c). In step a), a compound of Formula (5) or a salt thereof is contacted with a compound of Formula (II) or a salt thereof in the presence of a base to form a product, and in step b) the product formed in step a) is contacted with a compound of Formula (III) or a salt thereof in the presence of a base.
After forming the compound of Formula (I), the process includes washing the compound of Formula (I) from step b) with a solvent comprising water and a base to provide the compound of Formula (I) or a salt thereof. The claimed and described scope includes low impurity levels associated with Formula (5), with purity defined by HPLC, and a stated high-purity/composition profile for Formula (I) and Formula (IV).
Claims Coverage
The document includes independent claim coverage directed to a process for preparing a compound of Formula (8) or a salt using a defined sequence of intermediate conversions and a water/base washing step. The inventive features are organized around sequential contacting steps that form Formula (I) and then convert it to Formula (8) by hydrolysis, with defined R1 and R2 embodiments and impurity and purity constraints.
Sequential contacting of Formula (5), Formula (II), and Formula (III) to form Formula (I)
A process in which the compound of Formula (I) or a salt thereof is prepared by contacting a compound of Formula (5) or a salt thereof with a compound of Formula (II) or a salt thereof in the presence of a base, and then contacting the product formed in step a) with a compound of Formula (III) or a salt thereof in the presence of a base, wherein R1 is C1-4 alkyl, CH2Cl, phenyl, or benzyl and R2 is C1-4 alkyl.
Hydrolysis of Formula (I) to obtain Formula (8)
The process includes contacting a compound of Formula (I) or a salt thereof with a hydrolyzing agent to prepare a compound of Formula (8) or a salt thereof.
Water and base washing to provide Formula (I)
The process includes washing the compound of Formula (I) from step b) with a solvent comprising water and a base to provide the compound of Formula (I) or a salt thereof.
Impurity-selectivity constraint for Formula (5) within Formula (I)
The process includes that the compound of Formula (I) contains less than about 0.5% of the compound of Formula (5).
Purity threshold for the compound of Formula (8)
The process is characterized by having the compound of Formula (8) with a purity of at least 99%.
The claim coverage centers on sequential base-promoted contacting steps to form Formula (I), followed by hydrolysis and washing using a solvent comprising water and a base, with explicit R1 and R2 embodiments and with impurity and purity constraints tying Formula (5) content in Formula (I) and the purity of the compound of Formula (8).
Stated Advantages
The process is described as improved.
Low impurity levels associated with Formula (5) are described.
A high-purity/composition profile for Formula (I) and Formula (IV) is described.
The impurity control is presented as enabling the use of the target material without further purification in a downstream example.
Documented Applications
The process is framed for vadadustat and pharmaceutically acceptable salts.
The target material is used without further purification in a downstream example.
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