Synthesis of azo bonded immunoregulatory compounds
View Patent ↗Methods are disclosed for preparing compounds of Formula I: where R 1 , R 3 , and R 4 are independently hydrogen or C 1 to C 4 alkyl, and R 2 is: where R 5 is selected from the group consisting of hydrogen and C 1 to C 4 alkyl, or where R 6 , R 7 and R 8 are independently hydrogen or C 1 to C 4 alkyl; or the esters or pharmacologically acceptable salts thereof. The compounds and or their metabolites can be used to treat or prevent various diseases, particularly inflammatory conditions of the GI tract.
1. A method for preparing a compound of the formula:
where R 1 , and R 3 are selected from the group consisting of H, CH 3 , CH 2 CH 3 , and CH(CH 3 ) 2 ;
R 4 is H and R 2 is:
where R 5 , R 6 , R 7 and R 8 are independently hydrogen or C 1 to C 4 alkyl; or the esters or pharmaceutically acceptable salts thereof, comprising:
converting a compound of one of the following formulas:
to a diazonium salt;
reacting the diazonium salt with a compound of one of the following formulas:
hydrolyzing the nitrile or amide group to form a carboxylic acid group, and
optionally forming an ester or pharmaceutically acceptable salt of one or more of the carboxylic acid groups.
2. The method of claim 1 , wherein the aniline starting material is formed by reducing a nitrobenzene of one of the following formulas:
3. The method of claim 1 , wherein the nitrile or amide is hydrolyzed to the carboxylic acid using acid catalysis.
4. The method of claim 1 , wherein the nitrile or amide is hydrolyzed to the carboxylic acid using basic catalysis.
5. The method of claim 1 , wherein the nitrile or amide is hydrolyzed to the carboxylic acid using enzymatic catalysis.
6. The method of claim 1 , wherein R 6 , R 7 , and R 8 are independently selected from the group consisting of H, CH 3 , CH 2 CH 3 , and CH(CH 3 ) 2 .
7. The method of claim 1 , wherein R 5 is selected from the group consisting of H, CH 3 , CH 2 CH 3 , and CH(CH 3 ) 2 .
8. The method of claim 1 , wherein the compound that is formed is 5-(4-carboxymethyl-phenylazo)-2-hydroxy-benzoic acid, 5-[4-(1-carboxy-ethyl)-phenylazo]-2-hydroxy-benzoic acid or 4-(4-carboxymethyl-phenylazo)-phenylacetic acid.