Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di

Details Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di

1987-08-07

1989-02-21

Rotman, Alan L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546156, C07F 502, C07F 504, C07D21556

Patent

active

048066451

DESCRIPTION:

BRIEF SUMMARY
This invention relates to new Amifloxacine intermediates and a process for the preparation thereof. More particularly it is concerned with new anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and boric acids.
Ethyl-6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-dihydro-quinoline-3-carboxy late is an intermediate useful in the preparation of the antibacterial agent 6-fluoro-1-methylamino-7-(4-methyl-piperazino)-4-oxo-1,4-dihydro-qui noline-3-carboxylic acid (Journal of Medicinal Chemistry, 27, 1103, (1984). The latter compound can be prepared in two steps from ethyl-6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-dihydro-quinoline-3-carbox ylate. The said ester is subjected to hydrolysis whereupon the 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid thus obtained is reacted in the presence of a solvent at a temperature above 100.degree. C. with 1-methyl-piperazine for 15-22 hours to yield the desired 6-fluoro-1-methylamino-7-(4-methylpiperazino)-4-oxo-1,4-dihydro-quinoline- 3-carboxylic acid (European patent specification No. 90,424; Japanese patent specification No. 84 01,468).
It has been found that the 6-fluoro-1-methylamino-7-(4-methyl-piperazino)-4-oxo-1,4-dihydro-quinoline -3-carboxylic acid can be prepared under milder reaction conditions during a shorter reaction time by reacting 1-methyl-piperazine with a compound of the Formula I.
According to an aspect of the present invention there are provided new compounds of the Formula I ##STR5## (wherein R and R.sup.1 stand for halogen; an aliphatic acyloxy group comprising 2-6 carbon atoms and optionally substituted by halogen; or an aromatic acyloxy group comprising 7-11 carbon atoms).
According to a further aspect of the present invention there is provided a process for the preparation of the compounds of the Formula I (wherein R and R.sup.1 stand for halogen; an aliphatic acyloxy group comprising 2-6 carbon atoms and optionally substituted by halogen; or an aromatic acyloxy group comprising 7-11 carbon atoms), which comprises
(a) reacting the quinoline-3-carboxylic acid derivative of the Formula II ##STR6## with fluoroboric acid of the Formula IV or a trihalo borate of the Formula V derivative of the Formula VI ##STR7## (wherein R.sup.3, R.sup.4 and R.sup.5 stand for alkyl comprising 1-4 carbon atoms and optionally substituted by halogen; or aryl comprising 6-10 carbon atoms); or
(b) reacting a quinoline derivative of the Formula III ##STR8## (wherein R.sup.2 stands for hydrogen or alkyl comprising 1-4 carbon atoms) with fluoro boric acid of the Formula IV, or a trihalogeno borate of the Formula V (wherein X has the same meaning as stated above) or a triacyloxy borate of the Formula VI (wherein R.sup.3, R.sup.4 and R.sup.5 are as stated above).
As compound of the Formula V borone trifluoride, boron tribromide or boron trichloride or a complex or aqueous solution thereof can be used. One may preferably use a complex formed with an ether or alcohol (e.g. a complex of boron trifluoride formed with tetrahydrofuran, diethyl ether, methanol, or propanol). One may preferably use a solution of a boron trihalide formed with an aliphatic hydrocarbon (e.g. dichloro methane) or a carboxylic acid (e.g. acetic acid, trifluoro acetic acid or propionic acid).
The boric acid of the Formula IV, the boron trihalide of the Formula V or the compound of the Formula VI can be used in a molar ratio of 1-50-- preferably 1-5-- related to 1 mole of the compound of the Formula II or III. The above molar ratio is however but a preferable feature and an other molar ratio may be applied as well.
The above reactions may be carried out, if desired, in the presence of a solvent. As solvent e.g. water, ketones (e.g. acetone, methyl-ethyl-ketone), hydrocarbons (e.g. hexane, benzene, toluene), ethers (e.g. diethyl ether, dioxane, tetrahydrofuran), organic acids (e.g. acetic acid, propionic acid, trifluoro acetic acid, etc.) may be used.
The reactions can be carried out at room temperature, if desired.
On raising the reaction tempe

REFERENCES:
patent: 4182880 (1980-01-01), Watanabe et al.
Chemical Abstracts vol. 103(15) Abst. No. 103:123491p, Oct. 14, 1985.
Chemical Abstracts vol. 105(17), Abst. No. 153,293j, Oct. 27, 1986.

Affiliated with

Also associated with

Rating

Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Boric anhydrides of 6-fluoro-7-chloro-1-methylamino-4-oxo-1,4-di will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1523116