Process for the manufacture of quinoline derivatives

• US 20050215586A1
• Filed: 03/21/2005
• Published: 09/29/2005
• Est. Priority Date: 06/12/2002
• Status: Active Grant

• Current Assignee: Active Biotech AB
• Original Assignee: Active Biotech AB
• Inventors: Jansson, Karl
• Granted Patent: US 7,560,557 B2
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4

Abstract

A process for the preparation of the compounds of general formula (I) wherein R is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl;

• • R₅ is selected from methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, methylthio, ethylthio, n-propylthio, methylsulphinyl, ethylsulphinyl, fluoro, chloro, bromo, trifluoromethyl, and OCH_xF_y; wherein x=0−2, y=1−3 with the proviso that x+y=3; R₆ is hydrogen; or R₅ and R₆ taken together are methylenedioxy; R′ is selected from hydrogen, methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and OCH_xF_y, wherein x=0−2, y=1−3 with the proviso that x+y=3; R″ is selected from hydrogen, fluoro and chloro, with the proviso that R″ is selected from fluoro and chloro only when R′ is selected from fluoro and chloro; by reacting a quinoline-3-carboxylic acid ester derivative of formula A, where Z is methyl, with an aniline derivative of formula B according to the following reaction diagram, to give the compound of general formula (I), designated “C”, and an alcohol, designated “D”. in a solvent selected from straight or branched alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200° C.

Claims

1. A process for the preparation of a compound of general formula (I)

2. The process according to claim 1 wherein the solvent is n-heptane, n-octane or mixtures thereof.

3. The process according to claim 1 wherein the solvent is cis,trans-decahydronaphthalene.

7. The process according to claim 1 for the preparation of N-ethyl-N-phenyl-1,2-dihydro-5-ethyl-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide using a mixture of n-heptane and n-octane as a solvent.

4-6. -6. (canceled)

8. A process for the preparation of a compound of general formula (I)

9. The process according to claim 8 for the preparation of N-ethyl-N-phenyl-1,2,-duhydro-5-ethyl-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide.