Process for preparing [(3-hydroxypyridine-2-carbonyl)amino] alkanoic acids, esters and amides
Inventors
Lanthier, Christopher M. • Gorin, Boris • Oudenes, Jan • Dixon, Craig Edward • Lu, Alan Quigbo • Copp, James Densmore • Janusz, John Michael
Assignees
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Publication Number
US-10738010-B2
Publication Date
2020-08-11
Expiration Date
Abstract
Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.
Core Innovation
The disclosure describes catalytic processes for preparing 5-aryl- or 5-heteroaryl-substituted 3-hydroxypyridine-2-carbonyl amino acids, 5-aryl or heteroaryl-3-hydroxypicolinic acid intermediates, and ester or amide prodrugs. An aryl or heteroaryl precursor couples with a dihalo cyanopyridine to produce a substituted halo cyanopyridine intermediate; [procedural detail omitted for safety]. The claims encompass a general aryl-substituted preparation process alongside a specifically identified chlorophenyl-substituted intermediate embodiment.
The disclosed compounds serve as prolyl hydroxylase inhibitors that stabilize HIF-2α, wherein the ester and amide prodrugs hydrolyze to corresponding acids. The provided disclosure omits the background section, so the problem being solved is not explicitly described in patent. Associated reaction sequences and specific laboratory details are [procedural detail omitted for safety].
Claims Coverage
The claim coverage comprises two independent claims directed to catalytic processes for preparing aryl-substituted cyanopyridine compounds, presenting two inventive features.
Preparation of a substituted cyanopyridine intermediate
Claim 1 covers a catalyst-mediated coupling process for preparing a substituted cyanopyridine intermediate using a meta-substituted aryl or aryl boronic acid precursor and a dihalo cyanopyridine starting material; [procedural detail omitted for safety].
Preparation of a chlorophenyl-substituted cyanopyridine intermediate
Claim 6 covers a catalyst-mediated process for preparing a specified chlorophenyl-substituted cyanopyridine or picolinonitrile intermediate from an aryl boronic acid precursor and a dihalo cyanopyridine; [procedural detail omitted for safety].
The independent claims cover a general aryl-substituted intermediate preparation process and a specifically identified chlorophenyl-substituted embodiment, while dependent claims further specify catalyst and base choices and encompass downstream intermediate conversions; [procedural detail omitted for safety].
Stated Advantages
Not explicitly described in patent.
Documented Applications
Prolyl hydroxylase inhibitors that can stabilize HIF-2α.
Preparation of prolyl hydroxylase inhibitors and ester or amide prodrugs.
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