Processes for the preparation of 1,2,4-oxadiazole benzoic acids
View Patent ↗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.
1. A process for preparing a compound of the formula:
or a pharmaceutically acceptable salt thereof, comprising performing the following steps without isolation of an intermediate:
(1) reacting the cyanobenzoic acid methyl ester:
with hydroxylamine, to give:
followed by (2) acylation with 2-fluorobenzoyl chloride, to give:
followed by (3) condensation.
2. The process of claim 1 , wherein steps (1)-(3) are carried out in the same organic solvent.
3. The process of claim 2 , wherein the solvent is tert-butanol.
4. The process of claim 1 , further comprising:
(4) hydrolysis of the methyl ester of a compound of the formula:
to give:
or a pharmaceutically acceptable salt thereof.
5. A process for preparing a compound of the formula:
or a pharmaceutically acceptable salt thereof, comprising performing the following steps in the same organic solvent:
(1) reacting the cyanobenzoic acid methyl ester:
with hydroxylamine, to give:
followed by (2) acylation with 2-fluorobenzoyl chloride, to give:
followed by (3) condensation.
6. The process of claim 5 , wherein the solvent is tert-butanol.
7. The process of claim 5 , further comprising:
(4) hydrolysis of the methyl ester of a compound of the formula:
to give:
or a pharmaceutically acceptable salt thereof.
8. The process of claim 7 , wherein the hydrolysis is carried out in tert-butanol.