Preparation of pyridonecarboxylic acid antibacterials
View Patent ↗A process for making 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, and therapeutically acceptable salts thereof, and intermediates used in the process are disclosed.
1. A process for making 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, or a salt thereof, comprising:
(k) reacting a compound having formula (VII)
or a salt thereof,
wherein R 4 is alkyl,
wherein R 5 is hydrogen or C(O)R 6 , wherein R 6 is alkyl, phenyl or naphthyl, each of which is unsubstituted or substituted with one or two or three of independently selected OCH 3 , OCH 2 CH 3 , F, Cl or Br,
and a chlorinating agent and isolating or not isolating the product; and
(l) reacting the product of step (k) and a hydroxide base.
2. The process of claim 1 , further comprising isolating the product of step (l).
3. The process according to claim 1 , wherein the chlorinating agent is N-chlorosuccinimide, thionyl chloride, Cl 2 , Cl 2 O, or 1,3-dimethyl-5,5-dichlorohydantoin, with or without water, and with or without an acid.
4. The process according to claim 3 , wherein the chlorinating agent is N-chlorosuccinimide.
5. The process according to claim 3 , wherein the chlorinating agent is thionyl chloride.
6. The process according to claim 3 , wherein the chlorinating agent is Cl 2 .
7. The process according to claim 3 , wherein the chlorinating agent is Cl 2 O.
8. The process according to claim 3 , wherein the chlorinating agent is 1,3-dimethyl-5,5-dichlorohydantoin.
9. The process according to claim 3 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
10. The process according to claim 4 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
11. The process according to claim 5 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
12. The process according to claim 6 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
13. The process according to claim 7 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
14. The process according to claim 8 , with an acid wherein the acid is sulfuric acid, phosphoric acid, trifluoroacetic acid, or perchloric acid.
15. The process according to claim 1 , wherein the hydroxide base is the hydroxide base of sodium, potassium, lithium, barium, or mixtures thereof.
16. The process according to claim 1 , wherein the hydroxide base is potassium hydroxide.
17. The process according to claim 3 , wherein the hydroxide base is the hydroxide base of sodium, potassium, lithium, barium, or mixtures thereof.
18. The process according to claim 3 , wherein the hydroxide base is potassium hydroxide.
19. The process according to claim 9 , wherein the hydroxide base is the hydroxide base of sodium, potassium, lithium, barium, or mixtures thereof.
20. The process according to claim 9 , wherein the hydroxide base is potassium hydroxide.