CS235197B1 - Process for preparing 4,9-dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinolines - Google Patents

Abstract

The invention relates to a new process for the preparation of 4,9-dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo-[3,4-b]quinolines, characterized in that the disodium salt of 4,9-dihydro-3-methyl-4-oxo-1H-pyrazolo[3,4-b]quinolines is alkylated in dimethylformamide with methyl iodide at a temperature of 0 to 30 °C, preferably at a temperature of 20 °C, the barrel reaction mixture is crystallized from methanol, ethanol or n-propanol, preferably from ethanol, and the resulting mixture of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo[3,4-b]quinolines and 4,9-dihydro-2,3,9-trimethyl-4-oxo-2H-pyrazolo·-[3,4-b]quinolines is heated with pyridine hydrochloride at a temperature of 200 to 240°C, preferably at a temperature of 220°C.

Description

The invention relates to a novel preparation process

4,9-dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline, characterized in that the 4,9-dihydro-3-methyl-4-oxo disodium is alkylated -1H-pyrazolo [3,4-b] quinoline in dimethylformamide with methyl iodide at 0 to 30 ° C, preferably at 20 ° C, the keg reaction mixture is crystallized from methanol, ethanol or n-propanol, preferably ethanol, and formed a mixture of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline and 4,9-dihydro-2,3,9-trimethyl-4-oxyl The -2H-pyrazolo [3,4-b] quinoline is heated with pyridine hydrochloride at 200 to 240 ° C, preferably 220 ° C.

The invention relates to a novel preparation process

4,9-Dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline of formula I

Said compound of formula (I) serves as an intermediate for the preparation of biologically important substances, in particular having antiviral activity (U.S. Pat. No. 235 168).

Said compound of formula (I) is a known substance, the preparation of which is characterized by heating 4- (2-fluorophenyl) -6,8-dihydro-1,3,8-trimethylpyrazolo [3,4-e] (1). 4) diazepin-7 (1H) on with pyridine hydrochloride at 210-215 ° C [DeWald HA: J. Heterocyclic Chem. 11, 1061 (1974)].

Said compound of formula (1) was prepared by the process of the invention, characterized in that a mixture of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline and 4,9-dihydro- 2,3,9-trimethyl-4-oxo-2H-pyrazolo [3,4-b] quinoline is heated with pyridine hydrochloride at 200 to 240 ° C, preferably at 220 ° C. A mixture of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline and

According to the invention, 4,9-dihydro-2,3,9-trimethyl-4-oxo-2H-pyrazolo [3,4-b] quinoline can be prepared by recrystallizing the crude reaction mixture obtained by alkylation of 4,9-dihydro-3-methyl disodium salt. -4-oxo-1H-pyrazolo [3,4-b] quinoline in dimethylformamide with methyl iodide in 0.1 to 0.3 molar excess, preferably with an excess of 0.2 molar, at 0 to 30 ° C, preferably at 20 Deň: 32 ° C. Methanol, ethanol, n-propanol, preferably ethanol can be used to crystallize the crude reaction mixture.

Since the preparation of the starting 4,9-dihydro-3-methyl-4-oxo-1H-pyrazolo [3,4-b] quinoline is much easier than the preparation of 4- (2-fluorophenyl) 6,8-dihydro-1,3,8- trimethylpyrazolo [3,4-e] (1,4) diazepin-7- (1H) -one and easier than the preparation of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo [3,4-a] b-quinoline and 4,9-dihydro-2,3,9-trimethyl-4-oxo-2H-pyrazolo [3,4-b] quinoline, which may also be formed as intermediates for the preparation of the compound of formula I, shows the advantageous advantage of preparing the compound of formula The method according to the invention.

The following exemplary embodiment illustrates the invention but does not limit it in any way.

Example

4,9-Dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-bquinoline]

To a stirred suspension of 9.96 g of 4,9-dihydro-3-methyl-4-oxo-1H-pyrazolo [3,4-b] quinoline (50 mmol) in 200 ml of dimethylformamide was added 3.6 g of 80% sodium hydride. and the mixture was stirred under nitrogen at 20 ° C for 3 hours. After dropwise addition of 21.3 g of methyl iodide (0.15 mol), the mixture was stirred for 8 hours at 20 DEG C. The reaction mixture was evaporated to dryness and the residue was recrystallized from ethanol to give 7.2 g of a mixture which was ° C was added to pyridine hydrochloride obtained by gradually heating a mixture of pyridine (70 ml) and concentrated hydrochloric acid (105 ml) to 160 ° C. The reaction mixture was then stirred at 220 ° C for 2 hours to give 5.1 g (47.8 g). mp 248-249 ° C.

Claims (1)

SUBJECT A process for the preparation of 4,9-dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline, characterized in that the disodium salt of 4,9-dihydro-3-methyl-4 is alkylated. -oxo-1H-pyrazolo [3,4-b] quinoline in dimethylformamide with methyl iodide in 0.1 to 0.3 molar excess, preferably in excess of 0.2 molar, at 0 to 30 ° C, preferably at 20 ° C The crude recrystallization action is crystallized from methanol, ethanol or n-propanol, preferably ethanol, and the resulting mixture of 4,9-dihydro-1,3,9-trimethyl-4-oxo-1H-pyrazolo [3,4-b] of quinoline and 4,9-dihydro-2,3,9-trimethyl-4-oxo-2H-pyrazolo [3,4-b] quinoline are heated with pyridine hydrochloride at 200 to 240 ° C, preferably at 220 ° C.