# US 10,246,416 B2 · Process for preparing [(3-hydroxypyridine-2-carbonyl)amino] alkanoic acids, esters and amides

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,246,416 B2
- Document ID: US10246416B2
- Status: Granted
- Kind: B2
- Application number: 15/692,255
- Filed: 2017-08-31
- Published: 2017-12-21
- Granted: 2019-04-02
- Earliest claimed: 2011-06-06
- Assignees: Akebia Therapeutics, Inc.
- Applicants: Akebia Therapeutics, Inc.
- Inventors: Christopher M. Lanthier; Boris Gorin; Jan Oudenes; Craig Edward Dixon; Alan Quigbo Lu; James Denmore Copp; John Michael Janusz
- Web page: https://patentgrep.com/patent/US10246416B2

## CPC

- C07D 213/81: Amides; Imides
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 19/00: Drugs for skeletal disorders
- A61P 27/02: Ophthalmic agents
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/79: Acids; Esters
- C07D 213/803: Processes of preparation
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

A compound having the formula:
or a pharmaceutically acceptable salt thereof,
wherein A is a ring selected from:
2,3-difluorophenyl, 3,4-difluoro-phenyl, 3,5-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 3-bromophenyl, 3,5-dichlorophenyl, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenyl 2,3,6-trifluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trifluorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl, 2,3,6-trichlorophenyl, 2,4,5-trichlorophenyl, 3,4,5-trichloro-phenyl, 2,4,6-trichlorophenyl, 2-chloro-3-methylphenyl, 2-chloro-4-methylphenyl, 2-chloro-5-methylphenyl, 2-chloro-6-methylphenyl, 3-chloro-2-methylphenyl, 3-chloro-4-methylphenyl, 3-chloro-5-methylphenyl, 3-chloro-6-methyl-phenyl, 2-fluoro-3-methylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-5-methylphenyl, 2-fluoro-6-methylphenyl, 3-fluoro-2-methylphenyl, 3-fluoro-4-methylphenyl, 3-fluoro-5-methylphenyl, and 3-fluoro-6-methylphenyl;
Z is independently chloro or bromo; and
R10 is absent.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein Z is chloro.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein Z is bromo.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein ring A is selected from 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 3,4-difluoro-phenyl, 3,5-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromo-phenyl, 3,5-dichlorophenyl, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trifluorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl, 2,3,6-trichlorophenyl, 2,4,5-trichlorophenyl, 3,4,5-trichloro-phenyl, and 2,4,6-trichlorophenyl.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein ring A is selected from 2-chloro-3-methylphenyl, 2-chloro-4-methylphenyl, 2-chloro-5-methylphenyl, 2-chloro-6-methylphenyl, 3-chloro-2-methylphenyl, 3-chloro-4-methylphenyl, 3-chloro-5-methylphenyl, 3-chloro-6-methyl-phenyl, 2-fluoro-3-methylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-5-methylphenyl, 2-fluoro-6-methylphenyl, 3-fluoro-2-methylphenyl, 3-fluoro-4-methylphenyl, 3-fluoro-5-methylphenyl, and 3-fluoro-6-methylphenyl.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein ring A is 3-chlorophenyl or 3-chloro-6-methylphenyl.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein ring A is 3-chlorophenyl.

### Claim 8 (depends on 1)

The compound according to claim 1, having the structure,

### Claim 9 (depends on 1)

The compound according to claim 1, wherein the compound is a pharmaceutically acceptable salt of the compound having the structure,