RU2001110171A

RU2001110171A - IMPROVED METHOD FOR PRODUCING THIAZOLIDIN-2, 4-DIONE DERIVATIVES

Info

Publication number: RU2001110171A
Application number: RU2001110171/04A
Authority: RU
Inventors: Прабхакар ЧЕБИЙЯМ; Райендер Кумар ПОТЛАПАЛЛИ; Чинна Бакки Редди ГАДЕ; Баларам Маханти САТИШ; Рамабхадра Сарма МАМИЛЛАПАЛЛИ; Ом Редди ГАДДАМ
Original assignee: Др.Реддиз Лабораториз Лимитед
Priority date: 1998-09-14
Filing date: 1999-09-10
Publication date: 2003-05-27

Claims

1. The method of obtaining 5- [4 - [[3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl] methoxy] benzyl] thiazolidin-2,4-dione of the formula (1)

including

a) recovery of the compounds of formula (2 ')

where R represents a (C ₁ -C ₄ ) alkyl group,

and, if desired, re-esterification using sulfuric acid at a temperature of 0-60 ° C to obtain a compound of formula (3 ')

where R is as defined above,

b) hydrolysis of a compound of formula (3 ’) to produce an acid of formula (4)

c) condensation of an acid of formula (4) directly with N-methyl-anthranilamide of formula (7)

without any pre-activation of the acid to give a compound of formula (1) and, if desired,

d) converting a compound of formula (1) into pharmaceutically acceptable salts thereof.

2. The method according to claim 1, in which the compound of formula (3 ')

where R is as defined above,

directly condensed with N-methyl-anthranilamide of the formula (7)

to obtain the compounds of formula (1).

3. The method according to claim 1 or 2, in which the recovery is carried out using Raney nickel.

4. The method according to any one of claims 1 to 3, in which the recovery is carried out within 8-70 hours, preferably 12-24 hours

5. The method according to any one of claims 1 to 4, in which the recovery is carried out at a pressure of 1-41 atmospheres, preferably 1-27 atmospheres.

6. The method according to any one of claims 1 to 5, in which the recovery is carried out at a temperature of 15-70 ° C, preferably 30-60 ° C.

1. The method according to any one of claims 1 to 6, in which the purification of the crude recovered product is carried out using alcohol containing 1-4 carbon atoms, and then precipitated using water.

8. The method according to claim 1 or 2, in which the recovery in stage (a) is carried out using Mg in alcohol containing 1-4 carbon atoms.

9. The method according to any one of claims 1, 2, or 8, wherein the reduction in step (a) is carried out using 4-12 equivalents of Mg, preferably 8-10 equivalents, in an alcohol containing 1-4 carbon atoms.

10. The method according to any one of claims 1, 2, 8 or 9, in which the reaction temperature is 10-60 ° C, preferably 15-30 ° C.

11. The method according to any one of claims 1, 2, 8-10, in which the reaction time is 2-15 hours, preferably 6-8 hours

12. The method according to any one of claims 1, 2, 8-11, in which all magnesium salts are precipitated and filtered.

13. The method according to claim 1, in which the condensation reaction time in stage (C) is 6-20 hours, preferably 10-12 hours

14. The method according to claim 2, in which the reaction time is 5-30 hours, preferably 6-20 hours

15. The method according to claim 1 or 2, wherein in step (d) a pharmaceutically acceptable salt can be prepared by reacting a compound of formula (1) with potassium hydroxide in methanol, potassium carbonate or potassium t-butylate in the presence of a solvent to obtain a potassium salt of the compound formulas (1).

16. The method according to any one of claims 1, 2 or 15, in which the addition of potassium hydroxide in methanol or potassium carbonate is carried out at a temperature of 60-70 ° C.

17. The method according to any one of claims 1, 2, 15 or 16, in which, after adding potassium hydroxide or potassium carbonate, the reaction mixture is cooled to room temperature and incubated for 1 h at room temperature.

18. The method according to any one of claims 1, 2, 15-17, in which the solvent used is selected from a xylene / methanol mixture in a ratio of 1: 1.

19. A method of obtaining a compound of formula (2 '), including a). the interaction of p-hydroxybenzaldehyde of the formula (10)

with an alkyl haloacetate of formula (11)

where Hal represents a halogen atom such as fluorine, chlorine, or bromine;

R is as previously defined

in the presence of an aromatic hydrocarbon solvent, a base, an alkyl or arylsulfonic acid, and iodine to give a compound of formula (12)

and b) condensing a compound of formula (12), wherein R is as previously defined with a thiazolidine-2,4-dione of formula (13)

in the presence or absence of a solvent, using catalysts, to give a compound of formula (2 ').

20. The method according to claim 19, in which the aromatic hydrocarbon solvent used is selected from benzene, toluene, xylene or mixtures thereof.

21. The method according to claim 19 or 20, in which the base used is selected from both carbonates and bicarbonates of alkali and alkaline earth metals, such as potassium carbonate, potassium bicarbonate, sodium carbonate or calcium carbonate.

22. The method according to any one of claims 19-21, wherein the alkyl or arylsulfonic acid used is selected from methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, or p-nitrobenzenesulfonic acid.

23. The method according to any one of claims 19-22, wherein the reaction time in step (a) is 3-10 hours, preferably 5-7 hours.

24. The method according to any one of claims 19-23, wherein the reaction time in step (b) is 6-8 hours.

25. The method according to any one of claims 19-24, wherein the solvent in step (b) is selected from toluene and xylene.

26. The method according to any one of claims 19-25, wherein the catalysts in step (b) are selected from benzoic acid and piperidine.