Method for producing 4-oxoquinoline compound
The present invention provides a compound useful as a synthetic intermediate for an anti-HIV agent having an integrase inhibitory activity, and a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate. Specifically, for example, a compound represented by the formula (2′): wherein R is a fluorine atom or a methoxy group, and R 400 is a hydrogen atom or a C 1 -C 4 alkyl group, or a salt thereof, and a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate.
1. A method of producing a compound of the following formula (10):
or a salt thereof, comprising reacting a compound of the following formula (8):
wherein R 100 is a C 1 -C 4 alkyl group.
2. A method of producing a compound of the following formula (10):
or a salt thereof, comprising reacting a compound of the following formula (2-2-B):
wherein R 300 is a C 1 -C 4 alkyl group,
to produce a compound of the following formula (2-3-B):
or a salt thereof;
reacting said compound of formula (2-3-B), or a salt thereof, to produce a compound of the following formula (3-B):
reacting said compound of the formula (3-B) to produce a compound of the following formula (4-B):
wherein R 100 is a C 1 -C 4 alkyl group,
or a salt thereof;
reacting said compound of the formula (4-B) to produce a compound of the following formula (5-B):
wherein R 100 is a C 1 -C 4 alkyl group;
reacting said compound of the formula (5-B) to produce a compound of the following formula (6-B):
wherein R 100 is a C 1 -C 4 alkyl group;
reacting said compound of the formula (6-B) to produce a compound of the following formula (8):
wherein R 100 is a C 1 -C 4 alkyl group; and
reacting said compound of the formula (8) to produce the above compound of the formula (10) or a salt thereof.
3. A compound of the following formula (8):
wherein R 100 is a C 1 -C 4 alkyl group.
4. The compound according to claim 3 , wherein R 100 is ethyl.
5. The method according to claim 1 comprising subjecting the compound of formula (8) to hydrolysis.
6. The method according to claim 5 , wherein said hydrolysis occurs in the presence of a base.
7. The method according to claim 6 , wherein said base is selected from sodium hydroxide, potassium hydroxide, and lithium hydroxide.
8. The method according to claim 7 , wherein said base is sodium hydroxide.
9. The method according to claim 6 , wherein said base is present in an amount of 1 to 10 moles per 1 mole of the compound of formula (8).
10. The method according to claim 9 , wherein said base is present in an amount of 1 to 5 moles per 1 mole of the compound of formula (8).
11. The method according to claim 10 , wherein said base is present in an amount of 1 to 2 moles per 1 mole of the compound of formula (8).
12. The method according to claim 5 , wherein said hydrolysis occurs in the presence of an acid.
13. The method according to claim 12 , wherein said acid is selected from hydrochloric acid and sulfuric acid.
14. The method according to claim 5 , wherein said hydrolysis occurs in at least one solvent selected from methanol, ethanol, n-propanol, isopropanol, toluene, hexane, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,4-dioxane, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, N,N-dimethylformamide, dimethylsulfoxide, acetonitrile, and water.
15. The method according to claim 14 , wherein said hydrolysis occurs in ethanol and water.
16. The method according to claim 5 , wherein said hydrolysis occurs at 0° C. to 100 ° C.
17. The method according to claim 16 , wherein said hydrolysis occurs at 40° C. to 60° C.
18. The method according to any one of claim 1 or 5 - 17 , wherein R 100 is ethyl.