Processes for the preparation of 1,2,4-oxadiazole benzoic acids
AssigneePTC Therapeutics, Inc.
InventorsNeil G. Almstead, Peter Seongwoo Hwang, Seemon Pines, Young-Choon Moon, James J. Takasugi
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Abstract
Provided herein are processes for the preparation of compounds useful for the treatment, prevention or management of diseases associated with a nonsense mutation. More specifically, provided herein are processes for the synthesis of 1,2,4-oxadiazoles. In particular, provided herein are processes useful for the preparation of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid.
Claims15
A process for preparing a 1,2,4-oxadiazole benzoic acid or a pharmaceutically acceptable salt thereof comprising the steps of:
- (1) reacting a cyanobenzoic acid methyl ester with hydroxylamine;
- (2) acylation with a halobenzoyl chloride;
- (3) condensation;
- and
- (4) hydrolysis of the methyl ester,
- wherein each reaction step is carried out in the same organic solvent.
A process for preparing a compound of the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —(CH2CH2O)nR6 or any biohydrolyzable group;
- R6 is H or unsubstituted alkyl;
- X is at each occurrence independently F, Cl, Br or I;
- n is an integer from 1 to 7;
- and
- m is an integer from 1 to 5,
- comprising performing the following steps in the same solvent:
- (1) reacting the cyanobenzoic acid ester:
- with hydroxylamine, to give:
- followed by (2) acylation with a halobenzoyl chloride, to give:
- followed by (3) condensation.
Dependencies are inferred from the claim text.