Processes for the preparation of (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine
Provided herein are new processes for the preparation of aminosulfone intermediates for the synthesis of 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, which is useful for preventing or treating diseases or conditions related to an abnormally high level or activity of TNF-α. Further provided herein are processes for the commercial production of (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine.
1. A compound of Formula (IV):
or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein:
R is C 1 -C 6 alkyl;
R 1 is C 1 -C 6 alkyl;
each of R 2 , R 3 , R 4 , R 5 , and R 6 is at each occurrence independently hydrogen, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —CF 3 , —CN or —NO 2 ; and
Ar is aryl.
2. The compound of claim 1 , wherein the compound of Formula (IV) is racemic.
3. The compound of claim 1 , wherein the compound of Formula (IV) is the (+)- or (−)-enantiomer.
4. The compound of claim 1 , wherein R is —CH 3 ; R 1 is —CH 3 ; R 2 is H; R 3 is H; R 4 is —OCH 3 ; R 5 is —OCH 2 CH 3 ; R 6 is H; and Ar is phenyl.
5. The compound of claim 4 , wherein the compound is the hydrochloride salt.
6. The compound of claim 4 , wherein the compound is the isopropanol solvate hydrochloride salt.
7. The compound of claim 1 , wherein the compound is:
8. The compound of claim 7 , wherein the compound is the hydrochloride salt.
9. The compound of claim 7 , wherein the compound is the isopropanol solvate hydrochloride salt.