Chiral resolution method of N-[4-(1-aminoethyl)-phenyl]-sulfonamide derivatives

Patent metadata

Field	Value
Publication number	US-10479763-B2
Application number	US-201615325349-A
Country	US
Kind code	B2
Filing date	Feb 15, 2016
Priority date	Feb 17, 2015
Publication date	Nov 19, 2019
Grant date	Nov 19, 2019

Abstract

The present specification relates to a chiral resolution method of a stereoisomer mixture, comprising a step of mixing a stereoisomer mixture of compounds, in which an amine group is bound to an asymmetric carbon atom, with a chiral auxiliary and salt-forming auxiliary compound, wherein the chiral auxiliary is an O,O′-diacyltartaric acid derivative, more specifically, a 2,3-dibenzoyl-tartaric acid or O,O′-di-p-toluoyl tartaric acid, the salt-forming auxiliary compound is mandelic acid or camphorsulfonic acid, and an optical isomer having a high level of optical purity can be obtained by using the method. Therefore, according to one aspect of the present invention, the method can be useful in pharmaceutical or cosmetic field when preparing an optical isomer having a high optical purity.

First claim

The invention claimed is:

1. A method for chiral resolution of a mixture of stereoisomers of a compound of formula (I),

wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 is independently any one selected from a group consisting of H, —NH 2 , a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group and a halogen, and R 1 and R 2 are different from each other,
comprising mixing said mixture of stereoisomers of the compound of formula (I) with
(i) a chiral auxiliary; and
(ii) an auxiliary salt-forming compound
in the presence of a solvent, thereby precipitating a diastereomeric salt of said chiral auxiliary (i) with the compound of formula (I) in enantiomeric excess,
wherein the chiral auxiliary is one or more selected from a group consisting of 2,3-dibenzoyltartaric acid, O,O′-di-p-toluoyltartaric acid, a stereoisomer thereof, and a combination thereof, and the auxiliary sal-forming compound is one or more selected from a group consisting of mandelic acid, camphorsulfonic acid, a stereoisomer thereof, and a combination thereof.

2. The method according to claim 1 , wherein the chiral auxiliary is one or more selected from a group consisting of 2,3-dibenzoyltartaric acid, O,O′-di-p-toluoyltartaric acid, a stereoisomer thereof, and a combination thereof and the auxiliary salt-forming compound is one or more selected from a group consisting of mandelic acid, camphorsulfonic acid, a stereoisomer thereof, and a combination thereof.

3. The method according to claim 1 , wherein R 2 is hydrogen and an S enantiomer of the compound of formula (I) is obtained in enantiomeric excess when the chiral auxiliary is selected from a group consisting of the (−)-2,3-dibenzoyl-L-tartaric acid, (−)-O,O′-di-p-toluoyl-L-tartaric acid and a combination thereof.

4. The method according to claim 1 , wherein the auxiliary salt-forming compound is D-mandelic acid, L-mandelic acid, (1R)-(−)-10-camphorsulfonic acid, (1S)-(+)-10-camphorsulfonic acid or a combination thereof.

5. The method according to claim 1 , wherein the halogen is one or more selected from a group consisting of F, Cl, Br, and I.

6. The method according to claim 5 , wherein R 1 is selected from a group consisting of methyl, ethyl, propyl, butyl and pentyl and R 2 is hydrogen.

7. The method according to claim 6 , wherein R 1 is methyl, R 2 , R 3 and R 7 are hydrogen, and R 4 , R 5 and R 6 are independently selected from a group consisting of F, Cl, methyl, ethyl, and propyl.

8. The method according to claim 7 , wherein the compound of formula (I) is N-{4-[(1R/S)-1-aminoethyl]-2,6-difluorophenyl}methanesulfonamide.

9. The method according to claim 1 , wherein the solvent is one or more selected from a group consisting of water, a C 1-14 alcohol, acetic acid, nitromethane, propionic acid, formic acid and a combination thereof.

10. The method according to claim 9 , wherein the solvent is one or more selected from a group consisting of water, methanol, ethanol and isopropyl alcohol.

11. The method according to claim 10 , wherein the solvent is methanol, isopropyl alcohol or a combination thereof.

12. The method according to claim 1 , wherein the solvent is added at an amount to achieve complete dissolution of all reactants.

13. The method according to claim 12 , wherein the solvent is added at an amount of 5-15 times (v/w) of based on the total weight of the mixture of stereoisomers of the compound of formula (I).

14. The method according to claim 1 , wherein the mixing is performed at 40-70° C. or at the boiling point of the solvent or solvent mixture.

15. The method according to claim 1 , wherein the molar equivalent ratio of the chiral auxiliary to 1 molar equivalent of the mixture of stereoisomers is 0.10-0.5.

16. The method according to claim 15 , wherein the molar equivalent ratio of the chiral auxiliary to 1 molar equivalent of the mixture of stereoisomers is 0.2-0.3.

17. The method according to claim 1 , wherein the molar equivalent ratio of the auxiliary salt-forming compound to 1 molar equivalent of the mixture of stereoisomers is 0.5-1.5.

18. The method according to claim 17 , wherein the molar equivalent ratio of the auxiliary salt-forming compound to 1 molar equivalent of the mixture of stereoisomers is 0.75-1.5.

19. The method according to claim 1 , wherein the molar equivalent ratio of the chiral auxiliary and the auxiliary salt-forming compound together to 1 molar equivalent of the mixture of stereoisomers is 0.75-2.0.

20. A method for preparing a compound of formula (IIIa) or (IIIb)

wherein, each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 is independently any one selected from a group consisting of H, —NH 2 , a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group and a halogen, and R 1 and R 2 are different from each other, comprising
resolving the mixture of stereoisomers of the compound of formula (I) according to the method of claim 1 , and
converting the resulting stereoisomer to the compound of formula (IIIa) or (IIIb).

21. The method according to claim 20 , wherein the compound of formula (IIIa) is (R)—N-[1-(3,5-difluoro-4-methanesulfonamino-phenyl)-ethyl]-3-(2-propyl-6-trifluoromethyl-pyridine-3-yl)-acrylamide and the compound of formula (I) is N-{4-[(1R/S)-1-aminoethyl]-2,6-difluorophenyl}methanesulfonamide.

22. The method according to claim 20 , wherein said converting the resulting stereoisomer to the compound of formula (IIIa) or (IIIb) comprises coupling N-{4-[(1R)-1-aminoethyl]-2,6-difluorophenyl}methanesulfonamide (INT-3) with 3-(2-propyl-6-trifluoromethyl-pyridine-3-yl)-acrylic acid (INT-7).

Assignees

• Amorepacific Corp

Inventors

• Woo Byoung Young
• Lee Ki-Wha
• Shin Kwang-Hyun
• Park Miyoung
• Jung Kyoungmi
• Choi Joonho
• Choi Gyeyoung
• Cho Wonkyung
• Park Young-Ho

Classifications

• C07D213/56

  Amides · CPC title

• C07C303/44 Primary

  Separation; Purification · CPC title

• C07C311/08 Primary

  having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C303/36 Primary

  of amides of sulfonic acids · CPC title

• C07B57/00

  Separation of optically-active compounds · CPC title