Methoxymethyl-triphenylphosphonium chloride → 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-3-(2-hydroxyethyl)quinolin-4(1H)-one

428 mg of (methoxymethyl)triphenylphosphonium chloride was dissolved in 5 ml of THF, and 1.2 ml of 1.6 M n-butyl lithium hexane solution was added under ice-cooling in an atmosphere of argon, followed by stirring at the same temperature for 30 minute. A 5 ml THF solution of 178 mg of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbaldehyde was added under ice-cooling thereto, followed by stirring at the same temperature for 15 minutes and then stirring at room temperature for 3 hours. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. The resulting residue was dissolved in 10 ml of dioxane, and 5 ml of a 4 M hydrogen chloride dioxane solution was added, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into an ice-cooled aqueous saturated sodium hydrogen carbonate, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 239 mg of crude product of [7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]acetaldehyde was obtained. The resulting crude product was dissolved in 10 ml of ethanol, and 75 mg of sodium borohydride was added, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate, drying over anhydrous sodium sulfate and then concentration under a reduced pressure. The resulting residue was purified by silica gel column chromatography and crystallized from ethyl acetate to obtain 18 mg of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-3-(2-hydroxyethyl)quinolin-4(1H)-one.

1. temperaturecooling in an atmosphere of argon
2. temperaturecooling
3. stirringby stirring at the same temperature for 15 minutes
4. stirringstirring at room temperature for 3 hours
5. extractionfollowed by extraction with ethyl acetate
6. dry with materialdrying over anhydrous sodium sulfate
7. concentrationconcentration under a reduced pressure
8. dissolutionThe resulting residue was dissolved in 10 ml of dioxane
9. addition5 ml of a 4 M hydrogen chloride dioxane solution was added
10. stirringby stirring at room temperature for 2 hours
11. additionThe reaction mixture was poured into an ice-
12. temperaturecooled aqueous saturated sodium hydrogen carbonate
13. extractionfollowed by extraction with ethyl acetate
14. dry with materialdrying over anhydrous sodium sulfate
15. concentrationconcentration under a reduced pressure
16. customBy purifying the resulting residue by silica gel column chromatography, 239 mg of crude product of [7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]acetaldehyde
17. customwas obtained
18. stirringby stirring at room temperature for 1 hour
19. extractionfollowed by extraction with ethyl acetate
20. dry with materialdrying over anhydrous sodium sulfate
21. concentrationconcentration under a reduced pressure
22. customThe resulting residue was purified by silica gel column chromatography
23. customcrystallized from ethyl acetate

ORD record

ord-da6d198f541849e59bfbbd94ec116063

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629126B2