MXPA01005289A - Semi-hydrochloride of 8-cyan-1- cyclopropyl -7-(1s,6s-2 ,8-diazabicyclo [4.3.0]nonan -8-yl)-6- fluoro-1, 4-dihydro -4-oxo-3- quinoline carboxylic acid - Google Patents

Abstract

The invention relates to a semi-hydrochloride of 8-cyan-1- cyclopropyl -7-(1S, 6S-2,8- iazabicyclo [4.3.0]nonan -8-yl)-6- fluoro- 1,4 -dihydro- 4-oxo-3-quinoline carboxylic acid, to a method for producing this, and to an antibacterial agent containing the same. The 8-cyan-1- cyclopropyl -7-(1S, 6S-2, 8-diazabicyclo [4.3.0]nonan -8-yl)-6- fluoro-1, 4-dihydro-4- oxo-3-quinoline carboxylic acid can be described by formula (VI).

Description

_ SEM DROCLORIDE OF Ácroo 8-CYANO-I-CICLOPROPIL-7- (IS.6S-2.8-DIAZABICICL? R4.3.01-NONAN-8-IL) -6-FHJOR-1.4 DfflroRO-4-OXO-3- OUINOLINCARBOXÍLICO. FIELD OF THE INVENTION The present invention relates to an 8-cyano-l-cyclopropyl-7- (1S, 6S, 2, 8-diaza-bicyclo [4.3.0] nonan-8-yl) -6 -hydrochloride. -fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, to processes for its preparation as well as to the antibacterial agents containing it. 8-Cyano-l-cyclopropyl-7- (lS, 6S, 2,8-di-azabicyclo- [4.3.0] nonan-8-yl) -6-fluoro-l, 4-dihydro-4-oxo acid -3-quinoline-carboxylic acid of the formula (I) will be referred to below as CCDC.

Description of the prior art The CCDC is known from DE-A 19 633 805 or by PCT application No. 97 903 260.4. It is prepared by the reaction of 7-halogeno-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of the formula (II), REF: 129096 wherein Hal means fluorine or preferably chlorine, with (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane of the formula (III) in the presence of an auxiliary base in a suitable solvent. With CCDC of the formula (I), solutions of approximately 0.02% (w / w) in water can be prepared. This solubility is not sufficient for practical applications (solutions for injection or oral administration forms). It is known that many other quinolinecarboxylic acids are used in the form of certain salts for the formulations. As salts, metal salts of the quinoloncarboxylic acids (for example alkali carboxylates), on the other hand, acid addition products (protonated from basic centers in the amine radical of the substituted quinoloncarboxylic acids) can be used as salts. As such acid addition products, for example, mesylates, tosylates and hydrochlorides are frequently used. The hydrochlorides can be prepared in a particularly simple manner, they are pharmaceutically acceptable and have clearly better solubilities than those of the neutral compounds. The CCDC hydrochloride of the formula (IV) it is known from WO 97/31001. This can be characterized by means of its X-ray powder diffraction diagram, its differential thermal analysis (DTA) and its infrared spectrum.

(GO). The X-ray powder diffraction diagram shows the reflection layers indicated in Table 1 (2 Theta) of high and medium intensity (relative intensity> 30%). Table 1: X-ray powder diffraction diagram of the CCDC hydrochloride of the formula (IV) The X-ray powder diffraction diagram of the CCDC hydrochloride of the formula (IV) is also shown in Figure 1. The melting point of the CCDC hydrochloride of the formula (IV), determined with the aid of the DTA is from 305 ° C to 307 ° C (low decomposition). The additional thermal analysis diagram is depicted in Figure 2. The IR spectrum of the CCDC hydrochloride of the formula (IV) is shown in Figure 3. The CCDC hydrochloride of the formula (IV) can be prepared according to known methods At first. Thus, it is possible, for example, to combine a CCDC solution of the formula (I) in water with one molar equivalent of HCl and to evaporate the solution to dryness. Another method is to saponify the ethyl ester of 8-cyano-l-cyclopropyl-7- (lS, 6S, 2,8-diazabicyclo- [4.3.0] nonan-8-yl) -6-fluoro-1, 4 -dihydro-4-oxo-3-quinoline-carboxylic acid, of the formula (V) in aqueous hydrochloric acid and isolating the CCDC hydrochloride of the formula (IV) precipitated. With the CCDC hydrochloride of the formula (IV), a solution in water of approximately 2.8% (w / w) can be prepared. Thus, it is certainly more soluble in water than the CCDC of the formula (I), but not in a desirable amount for all the formulations. DETAILED DESCRIPTION OF THE INVENTION It has been found according to the invention that, surprisingly, the CCDC semihydrochloride of the formula (VI) It is soluble in water in an especially good way. With the CCDC semihydrochloride of the formula (VI), solutions in water at 19% (w / w) can be prepared. Thus, the object of the invention is the crystalline CCDC semihydrochloride of the formula (VI), which is characterized, among other things, by having a X-ray powder diffraction diagram with the reflection layers indicated in intensity table 2 superior and middle (relative intensity > 30%).

Tahla 2: X-ray powder diffraction diagram of the CCDC of the formula (SAW). 2 T (2 Theta) 5.86 6.90 7.26 8.98 9.35 10.13 10.68 10.97 12.41 13.67 14.57 14.89 15.73 16.07 16, 47 16.87 17.78 18.91 19.81 20.04 20.62 20.75 20.93 21.46 21.74 22.92 25.36 25.71 26.98 27.58 28.24 30 61 The X-ray powder diffraction diagram of the CCDC semihydrochloride of the formula (VI) is represented in the formula (VI). The CCDC semihydrochloride according to the invention of the formula (VI) is further characterized in that it has a melting point, determined by differential thermal analysis, from 278 ° C to 280 ° C. The corresponding differential thermal analysis diagram has been shown in Figure 5. The CCDC semihydrochloride according to the invention of the formula (VI) is further characterized by having an infrared spectrum, measured in KBr as shown in the figure 6. The CCDC semihydrochloride of the formula (VI) with an undetermined crystalline form can be prepared according to methods known in principle, for example if a solution of the CCDC of the formula (I) in water is combined with a semi-molar equivalent of HCl and The solution is concentrated by evaporation to dryness. In the same way it is possible in principle to stir such amounts of CCDC of the formula (I) and CCDC hydrochloride of the formula (TV) in molar proportions one by one in water in such a way that the total concentration is less than 20% . The solution obtained can be concentrated by evaporation to dryness. In addition, it has been found according to the invention that, surprisingly, a CCDC semihydrochloride of the formula (VI), which is characterized by means of the X-ray powder diffraction diagram and by means of the above-mentioned differential thermal analysis diagram, can be prepared directly. The object of the present invention is therefore also the CCDC semihydrochloride of the formula (VI), characterized in that the 7-halogen-non-8-cyano-l-cyclopropyl-6-fluoro-1,4 acid is reacted -dihydro-4-oxo-3-quino-lolcarboxylic acid of the formula (II), in which halogen means fluorine or preferably chlorine, with (1S, 6S) -2,8-diazabicyclo [4.3.0] nonane of the formula (III), if appropriate in the presence of a base, in one of the following diluents or mixtures of diluents: a) aliphatic alcohols with at least 4 carbon atoms such as for example butanol, isobutanol, 2-butanol, tertiary butanol , 1-pentanol. b) mixtures of aliphatic alcohols with at least 2 carbon atoms such as for example propanol, isopropanol, butanol, isobutanol, 2-butanol, tertiary butanol or 1-pentanol with the polar aprotic solvent N-methyl-pyrrolidone. c) mixtures consisting of propanol and N, N-dimethylformamide, or d) mixtures of ethanol with N-methyl-pyrrolidone with a base addition of tertiary amines such as for example tripropylamine, tributylamine N-ethylmorpholine, N-propylmorpholine and / or N-butylmorpholine. In the case of the preferred preparation variants with a diluent mixture according to b) or c), the mixing ratio is from 1: 1 to 3: 1 and in particularly preferred embodiments from 1: 2 to 2: 1. suitable bases are, according to the variants for obtaining diluents and diluent mixtures according to a) to c), tertiary amines such as for example triethylamine, tripropylamine, ethyldiisopropylamine (Hünig's base), tributylamine, N-ethylmorpholine, N-propylmorpholine and N -butylmorpholine. In the case of the production variants a) to d), embodiments in which an excess of (lS) is used are preferred., 6S) -2,8-diazabicyclo [4.3.0] nonane of the formula (III). In the case of the preparation variants according to a) to d), 1 mol of the compound of the formula (II) are preferably 1 to 2 mol of base, more preferably of 1.1 to 1.5 mol of base. The reaction in the case of the production variants according to a) to d) is carried out at normal pressure or at high pressure between 1 bar and 100 bar, preferably between 1 bar and 20 bar. The reaction in the case of the production variants according to a) to d) is carried out at temperatures between 0 ° C and 200 ° C, preferably between 20 ° C and 150 ° C. Preferably, 1 mol of compound (II) of 1 to 2 mol, particularly preferably 1 to 1.5 mol of compound (III) are used. The CCDC semihydrochloride of the formula (VI) is precipitated from the reaction mixture and can be separated by suction filtration. The solid product separated by suction filtration can be purified, if appropriate, by washing with the alcohol used in the reaction. The starting materials of formulas (II) and (III) for obtaining the CCDC are known (see DE-A 19 633 805). The CCDC semihydrochloride of the formula (VI) is active in an excellent manner against pathogenic bacteria in the field of human or animal medicine. Its broad field of application corresponds to that of the CCDC. The X-ray powder diffraction diagram for the characterization of the crystalline modifications of CCDC hydrochloride and CCDC semihydrochloride was obtained with a STADI-P transmission diffractometer with a position sensitive detector (PSD2) from Stoe. . The melting point of the differential thermal analysis was obtained with the 820 device from Mettler-Toledo. In this case, the sample was heated in an aluminum crucible at 20 K / minute to the air. The IR spectrum was obtained with the FTS 60 A device from the Biorad firm in KBr. The following examples illustrate the invention without limiting it. The diluents / base systems described in the following examples are especially excellent. Comparative example. Obtaining the CCDC hydrochloride of the formula (IV) 850 g of the ethyl ester of 8-cyano-1-cyclopropyl-7- (1S, 6S, 2, 8-diazabicyclo [4.3.0] nonan-8- il) -6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid in a mixture consisting of 1600 ml of water and 800 ml of 10% hydrochloric acid. The reaction mixture was heated to boiling, whereupon the ester was dissolved and then the product immediately began to precipitate, the suspension is heated for 3 hours to boiling. It is then allowed to cool to approximately 50 ° C and 1,500 ml of ethanol are added. The reaction mixture is cooled to 0 ° C and stirred at this temperature for 1 hour.

The solid product is separated by suction filtration, washed with another 1,000 ml of ethanol and dried at 60 ° C until constancy of weight. 845.5 g of a beige solid product are obtained. Elemental analysis (calculated values for C21H22CIFN4O3 hydrochloride, molecular weight 432.89): Carbon: found 58.2% (calculated 58.27%) hydrogen: found 5.1% (calculated 5, 12%) chlorine: found 8, 1% (calculated 8.19%).

The product shows the X-ray powder diffraction diagram shown in Figure 1, the differential thermal analysis diagram shown in Figure 2 and the IR spectrum represented in Figure 3. Obtaining the CCDC semihydrochloride of the formula (VI) . Example 1. 9.2 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are placed in a mixture of 30 ml of butanol, 18 ml of N-methyl-pyrrolidone and 4.85 g of Hünig's base. The mixture is refluxed and 4.17 g of (lS, 6S) -2,8-diazabicyclo [4,3,0] nonane are added dropwise. Once the dropwise addition is complete, stir for another 3 hours at reflux, allow to cool to room temperature, remove the solid product by suction filtration, wash it with a total of 20 ml of butanol and dry it at 60 to 70 ° C in the vacuum drying cabinet until weight constancy. 8.54 g of beige solid product are obtained, which shows the powder diffraction diagram with X-rays shown in figure 4, and the differential thermal analysis diagram shown in figure 5. Elemental analysis (values calculated for the semih? CCDC drochloride C2iH22, sClo, 5FN? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%). Ejm? 2. A mixture consisting of 9.2 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 60 ml of butanol is heated to reflux. and 4.85 g of Hünig base. 4.17 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 20 ml of butanol and dried to constant weight. They are obtained , 6 g of beige solid product, whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride of formula (VI). Elemental analysis (calculated values for the CCDC semihydrochloride C2iH22, sCo, 5FN? 3, molecular weight 414,658): Carbon: found 60.55% (calculated 60.83%) hydrogen: found 5.3% (calculated 5.23%) chlorine: found 4.2% (calculated 4.275%) nitrogen: found 13.5% (calculated 13.51%) oxygen: found 11.7% (calculated 11.58%). Example 3. A mixture of 4.6 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is heated to reflux, 15 ml of propanol, 9 ml of N-methyl-pyrrolidone and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of propanol and dried to constant weight. 4.6 g of beige solid product are obtained whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride. Elemental analysis (calculated values for the CCDC semihydrochloride:? H22, sClo, 5FN4? 3, molecular weight 414,658): Chlorine: found 4.3% (calculated 4.275%). Example 4. A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of isopropanol, is heated to reflux. ml of N-methyl-pyrrolidone and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 120 ml of isopropanol and dried to constant weight. 5.3 g of beige solid product are obtained. Elemental analysis (calculated values for the CCDC semihydrochloride C2iH22, sCo, 5FN4? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%).

A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclpyl-6-fluoro-1,4-dihydride-4-oxo-3-quinolinecarboxylic acid, 15 ml of 2-butanol is refluxed. , 9 ml of N-methyl-pyrrolidine and 2.42 g of Hünig's base. 2.08 g (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of 2-butanol and dried to constant weight. 5.48 g of beige solid are obtained whose differential technical analysis diagram corresponds to that of the CCDC semihydrochloride of the formula (VI). Elemental analysis (calculated values for the CCDC semihydrochloride C2iH22.5Clo, sFN4? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%). Example 6. A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclpyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is heated to reflux, 15 ml of isobutanol, 9 ml of N-methyl-pyrrolidine and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo- [4.3.0] -nonano are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration, washed with a total of 10 ml of isobutanol and dried to constant weight. 4.99 g of beige solid product are obtained, whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride of the formula (VI). Elemental analysis (calculated values for the CCDC semihydrochloride C2iH22.5? Or, 5FN4? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%).

A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclpyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of tertiary butanol is heated to reflux. 9 ml of N-methyl-pyrrolidine and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of heated tertiary butanol and dried to constant weight. 5.38 g of beige solid product are obtained, whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride of the formula (VI). Elemental analysis (calculated values for the CCDC semihydrochloride? H22,5Clo, sFN4? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%).

A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclpyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of 1- pentanol is heated to reflux. , 9 ml of N-methyl-pyrrolidine and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] -nonano are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of 1-pentanol and dried to constant weight. 3.0 g of beige solid product are obtained, whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride of the formula (VI). Elemental analysis (calculated values for CCDC half-hydrochloride C2iH22.5Clo, sFN4? 3, molecular weight 414,658): Chlorine: found 4.3% (calculated 4.275%).

A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclpyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of ethanol, is heated to reflux. ml of N-methyl-pyrrolidone and 3.47 g of tributylamine. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] -nonano are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of ethanol and dried to constant weight. 5.0 g of beige solid product are obtained, whose differential thermal analysis diagram corresponds to that of the CCDC semihydrochloride of the formula (VI). Elemental analysis (calculated values for the CCDC semihydrochloride C2iH22.5Clo, 5FN4? 3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%).

A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of ethanol is heated to reflux. -9 ml of N-methyl-pyrrolidine and 2.16 g of N-ethylmorpholine. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of ethanol and dried to constant weight. 5.4 g of beige solid product are obtained. Elemental analysis (calculated values for CCDC semihydrochloride C21H22, SCI0) SFN4O3, molecular weight 414,658): Chlorine: found 4.3% (calculated 4.275%). Example 11. A mixture consisting of 4.6 g of 7-chloro-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid is heated to reflux, 15 ml of propanol, 9 ml of N, N-dimethylformamide and 2.42 g of Hünig's base. 2.08 g of (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane are added dropwise and the mixture is subsequently stirred at reflux for 3 hours. The solid product is separated by suction filtration at room temperature, washed with a total of 10 ml of propanol and dried to constant weight. 4.4 g of beige solid product are obtained. Elemental analysis (calculated values for CCDC semihydrochloride C21H22) SC10 > 5FN4O3, molecular weight 414,658): Chlorine: found 4.2% (calculated 4.275%). It is noted that, with regard to this date, the best method known to the applicant, to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (11)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1.- 8-cyano-l-cyclopropyl-7- (lS, 6S-2,8-diazabicyclo- [4.3.0] semihydrochloride] ] nonan-8-yl) -6-fluoro-l, 4-dihydro-4-oxo-3-quinolinecarboxylic acid. 2.- 8-Cyano-l-cyclopropyl-7- (lS, 6S-2,8-diazabicyclo- [4.3.0] nonan-8-yl) -6-fluoro-l, 4-dihydro-4 acid semmihydrochloride -oxo-3-quinolinecarboxylic (CCDC semihydrochloride), characterized in that it presents a diagram of X-ray powder diffraction with the following reflection layers (2 Theta) of high and medium intensity.
2. 2 T (2 Theta) 5.86 6.90 7.26 8.98 9.35 10.13 10.68 10.97 12.41 13.67 14.57 14.89 15.73 16.07 16, 47 16.87 17.78 18.91 19.81 20.04 20.62 20.75 20.93 21.46 21.74 22.92 25.36 25.71 26.98 27.58 28.24 30 , 61 3.- 8-cyano-l-cyclo-propyl-7- (lS, 6S-2,8-diazabicyclo- [4.
3. 3.0] nonan-8-yl) -6-fluoro-l, 4 -hydrochloride -dihydro-4-oxo-3-quinolinecarboxylic acid (CCDC semihydrochloride), characterized in that it has a X-ray powder diffraction diagram with the following reflection layers (2 Theta) of high and medium intensity. 2 T (2 Theta) 5.86 6.90 7.26 8.98 9.35 10.13 10.68 10.97 12.41 13.67 14.57 14.89 15.73 16.07 16, 47 16.87 17.78 18.91 19.81 20.04 20.62 20.75 20.93 21.46 21.74 22.92 25.36 25.71 26.98 27.58 28.24 30 , 61 - - and from a melting point, detected by means of DTA from 278 ° C to 280 ° C. 4.- CCDC sepihydrochloride according to claim 1 or 2, characterized in that it is obtained by reacting 7-halogeno-8-cyano-l-cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-3-quinolinecarboxylic acid of the formula (II) wherein Hal means fluorine or chlorine, and (lS, 6S) -2,8-diazabicyclo [
4. 4.3.0] nonane of the formula (III) optionally in the presence of a base and in one of the following diluents or mixtures of diluents: a) aliphatic alcohols with at least 4 carbon atoms, b) mixtures of, for example, aliphatic alcohols with at least 3 carbon atoms with the diluent N-methyl-pyrrolidone, cc)) mixtures consisting of propanol and N, N-dimethylformamide, or d) mixtures of ethanol with N-methyl-pyrrolidone with a base addition of tripropylamine, tributylamine, N-ethylmorpholine, N-propylmorpholine and / or N-butylmorpholine.
5. 5. Process for obtaining the CCDC semihydrochloride according to one of claims 1 to 4, characterized in that the acid 7-halogeno-8-cyano-l-cyclopropyl-6-fluoro-1,4-dihydro-4 is reacted -oxo-3-quinolinecarboxylic acid of the formula (II) wherein Hal means fluorine or chlorine, and (lS, 6S) -2,8-diazabicyclo [4.3.0] nonane of the formula (III) optionally in the presence of a base and in one of the following diluents or mixtures of diluents: a) aliphatic alcohols with at least 4 carbon atoms, b) mixtures of, for example, aliphatic alcohols with at least 3 carbon atoms with the diluent N-methyl-pyrrolidone, c) mixtures consisting of propanol and N, N-dimethylformamide, or d) mixtures of ethanol with N-methyl-pyrrolidone with a base addition of tripropylamine, fributuamine, N-ethylmorphine, N-propylmorpholine and / or N-butylmorpholine.
6. 6. Process for obtaining the CCDC semihydrochloride according to claim 5, characterized in that an aliphatic alcohol with at least 4 carbon atoms is used as the diluent or an aliphatic alcohol with at least 2 atoms is used as a component of a mixture of diluents. of carbon.
7. 7. Process for obtaining the CCDC semihydrochloride according to claim 5, characterized in that when an aliphatic alcohol with at least 3 carbon atoms is used as a component of a mixture of diluents is used at the same time as an additional diluent, N -methyl-pyrrolidone in the ratio of 1 to 1 to 3 to 1.
8. 8.- Procedure for obtaining the CCDC semihydrochloride according to claim 6, characterized in that when propanol is used as a component of the moon mixture of diluents is used at the same time as an additional diluent N, N-dimethylformamide in the ratio of 1 to 1 to 3 to 1.
9. 9. A medicament characterized in that it contains, in addition to the usual auxiliary products and excipients, the CCDC semihydrochloride according to one of claims 1 to 4.
10. 10.- Use of the CCDC semihydrochloride according to one of claims 1 to 4, for the preparation of medicaments.
11. 11. Use of the CCDC semihydrochloride according to one of claims 1 to 4, in antibacterial agents.