CS252636B1 - O-substituted 4,9-dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1h-pyrazolo(3,4-b)quinolines - Google Patents

Abstract

The present invention relates to O-substituted 4,9-dihydro-6-hydroxy-3,9-dimethyl-4- -σχο-β-pyrazolo (3,4-b) quinolines of Formula I wherein R is hydrogen or methyl. These new, not yet described, substances are useful as intermediates for the preparation of substances showing significant \ t biological effects, especially antiviral and anti-tumor effect.

Description

The present invention relates to O-substituted 4,9-dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinolines of formula I

wherein R is hydrogen or methyl.

These novel substances, which have not been described yet, are useful as intermediates for the preparation of substances having significant biological effects, in particular antiviral and antitumor activity.

The compound of formula (I) wherein R is methyl can be prepared from the condensation product of 4- (4-methoxyphenyl) -4-methylthiosemicarbazide with ethyl 2-chloroacetate by cyclization with polyphosphoric acid at elevated temperature.

A compound of formula I wherein R is hydrogen may be prepared according to the invention from 4,9-dihydro-6-methoxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline by boiling demethylation azeotropic hydrobromic acid.

A compound of formula I wherein R is hydrogen may also be prepared according to the invention from 4,9-dihydro-6-methoxy-1,3,9-trimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline or from 4,9-dihydro-2,3,9-trimethyl-4-oxo-6-methoxy-2H-pyrazolo (3,4-b) quinoline by demethylation of pyridine hydrochloride at elevated temperature.

The method of preparation of the substances is simple, the products are obtained in satisfactory yields in a quality directly applicable for further processing.

Further details are given in the following examples. The examples given are merely illustrative and not limiting.

Example 1

4.9-Dihydro-6-methoxy-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline

To a stirred suspension of 4- (4-methoxyphenyl) -4-methyl-thiosemicarbazide (10.5 g, 50 mmol) in ethanol (250 mL) was added ethyl 2-chloroacetacetate (8.5 g, 52 mmol) with stirring. was stirred for 2 hours at room temperature and then boiled for 0.5 hours.

After filtration of the precipitated sulfur, the solution was evaporated to dryness and the residue was mixed with polyphosphoric acid (100 g, 85% ^P 2 ° 5 * ^{and SM} ® ^Sb y ^la stirred for 2 hours at 90 ° C. The reaction mixture was poured into water (1 000 ml), cooled, insoluble material was aspirated, recrystallized from ethanol to give 7.0 g (58%) of mp 317-332 ° C.

Example 2

4.9-Dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline

A mixture of 4,9-dlhydro-6-methoxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline (16.1 g, mmol) and azeotropic hydrobromic acid (265 mL) was boiled under reflux for hours. After cooling, the insoluble material was aspirated and recrystallized from ethylene glycol monomethyl ether. 14.1 g (93%) of m.p. Mp 343 - 348 ° C.

Example 3

4.9-Dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline

A stirred mixture of pyridine (20 g) and concentrated hydrochloric acid (30 mL) was gradually heated to 160 ° C. 4,9-Dihydro-6-methoxy-1,3,9-trimethyl-4-oxo-1H-pyrazolo (3,4-b) quinoline (5.1 g, 20 mmol) was added at this temperature and the mixture was Stirred at 220 ° C for 10 hours.

The mixture was poured into water (150 mL), boiled with activated carbon and filtered. The filtrate was cooled and the precipitated crystals were filtered off with suction, washed with water and recrystallized from ethanol. 1.1 g (22%) of m.p. Mp 343 - 348 ° C.

Example 4

4.9-Dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo [3,4-b] quinoline

A mixture of anhydrous pyridine hydrochloride (40 g) and 4,9-dihydro-6-methoxy-2,3,9-trimethyl-4-oxo-2H-pyrazolo (3,4-b) quinoline (2.0 g, 7, 8 mmol) was stirred under nitrogen at 220 ° C for 4 hours. The work-up described in Example 3 afforded 0.65 g (34%) of m.p. Mp 343 - 348 ° C.

Claims (1)

O-substituted 4,9-dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo (3,4-b) quinolines of formula I -CH ·, CH ₃ H (I), wherein R is hydrogen or methyl.