CS262300B1 - 5- [2- (N, N-Dimethylamino) ethoxy] -7- [3- (N, N-dimethylamino) propyl] -7-hydroxy-7H-bonzo / c / fluorone Oihydrochloride and Process for its Preparation - Google Patents

Abstract

The present invention relates to 5- [2- (N, N-dimethylamino) ethoxy] -7- [3- (N, N-dimethylamino) propyl] -7-hydroxy-7H- dihydrochloride. -benzo / c / fluorene, and a process for the preparation thereof consisting in the reaction of 5- [2- (N, N-dimethyl-amino) ethoxy] -7-oxo-7H-benzo / c / fluorene with 3- (N, N dimethylamino) propylmagnesium ium chloride. The substance is a potent inhibitor of tumor cell protein synthesis.

Description

The benzo (c) fluorene derivatives carry different pharmacological activities, depending on the position and type of substitution of the benzo (c) fluorene skeleton. (See AO 212 669, 212 670,

217,731,231,207). The antitumor effect demonstrated in animals with experimental tumors and leukemias is considered to be of particular importance. These effects are particularly pronounced for 5- [2- (/, Ν-dimethylamino) ethoxy] -7-oxo-7H-benzo [c] fluorene hydrochloride, the trade name Benfluron. Further details on biological effects are given in our article. AO 212 669. The compound of formula I at concentrations greater than 10 ^-6 mol.l ^-1 reduces the rate of incorporation (U- ¹⁴ C / amino acid mixture into the trichloroacetic acid precipitable Yoshide tumor cell fraction. IC value. "6.5.10 ^-6 mol .l ^-1 substance lies between the most potent inhibitor of protein synthesis from a group of cells with the basic benzo / c / fluorene skeleton.

According to formula II of the invention, the compound of formula I is prepared by reacting the substance

(II) with an agent of formula III

Cl-Mg-CH ₂ CH ₂ CH ₂ N (CH ₃ ) ₂ (III) used in an amount of 1.5 to 3 mol equivalents, preferably in an amount of 2 mol equivalents, in an environment of nucleophilic solvents, preferably tetrahydrofuran, at 70 ° C. The reaction of II with the reagent of formula III can be carried out in an environment of nucleophilic solvents such as diethyl ether, dibutyl ether, anisole, tetrahydrofuran; the use of tetrahydrofuran appears to be particularly advantageous in the course of the reaction.

After reaction with 20% aqueous ammonium chloride, the reaction mixture is not limited in any way after the solvent has been dried and evaporated.

processed by the usual procedure; for example, after decomposition, the organic portion is taken up in the chlorinated solvent and the crude product is purified by crystallization. More detailed from the following example, but the scope of the invention

Example

480 mg (0.02 mol) of magnesium is poured over 5 ml of dry tetrahydrofuran, a grain of iodine, a few drops of dibromoethane and a quarter of a solution of 2.43 g (0.02 mol) of 3- (Ν, ethy-dimethylamino) propyl chloride in 10 ml are added. dry tetrahydrofuran. After the start of the reaction, the remainder of the solution was added dropwise and the reaction mixture was stirred at 70 ° C until the magnesium disappeared. After this time, a solution of 3.17 g (0.01 mol) of 5- [2- (Ν, Ν-dimethylamino) ethoxy] -7-oxo-7H-benzo [c] fluorene in 10 ml of dry tetrahydrofuran was added and stirred at 70 ° C for 1.5 hours. The reaction mixture was quenched with 10 ml of 20% aqueous ammonium chloride solution, the organic portion was taken up in chloroform and, after drying over anhydrous sodium sulfate, the chloroform was evaporated. The residue was dissolved in ethanol and acidified with ethanolic hydrochloric acid to give a melting point of 219-222 ° C.

Claims (2)

1. 5- [2- (Ν, Ν-Dimethylamino ethoxy) -7- [3- (N, N-dimethylamino) propyl] -7-hydroxy-7H-benzo [c] fluorene dihydrochloride of the formula I HO CH ₂ CH ₂ CH ₂ N (CH ₃ ) ₂ 2. A process for the preparation of 5- [2- (N, N-dimethylamino) ethoxy] -7-3- (Ν, Ν-dimethylamino) propyl] -7-hydroxy-7H-benzo (c) fluorene dihydrochloride of the formula I according to item 1 characterized in that the compound of formula II and ₂ ch ₂ n (ch ₃ ) ₂ (II) are reacted with an agent of formula III Cl-Mg-CH ₂ -CH ₂ -CH ₂ N (CH ₃ ) ₂ (III) used in an amount of 1.5 to 3 mol equivalents, preferably in an amount of 2 mol equivalents, in an environment of nucleophilic solvents, preferably tetrahydrofuran, at 70 ° C .