Crystal form of derivative of aminomethyl caproic acid

Abstract

The invention discloses a crystal form of a derivative of aminomethyl caproic acid, and in particular discloses a compound with the following structural formula. The compound determined by an X-ray diffractometer in a diffraction pattern has diffraction peaks at about 9.05 degrees and the like. The compound provided by the invention can be used for auxiliary treatment of generalized anxiety disorder, diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia syndrome and epilepsia.

Description

technical field

[0001] The present invention relates to aminomethylhexanoic acid derivatives, especially (S)-3-(aminomethylhexanoic acid derivatives, which can be used for auxiliary treatment of generalized anxiety disorder, diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia syndrome and epilepsy )-A new crystal form of 5-methylhexanoic acid. Background technique

[0002] (S)-3-(aminomethyl)-5-methylhexanoic acid, commonly known as pregabalin, its molecular formula is C 8 h 17 NO 2 , the molecular weight is 159.23. Like gabapentin, pregabalin is a 3-substituted analog of gamma-aminobutyric acid (GABA), and their chemical structures are as follows:

[0003]

[0004] Pregabalin (pregabalin, trade name Lyrica, Lyrica) developed by Pfizer is a 3-position substituted analogue of γ-aminobutyric acid. ) related compounds and their intended successors. Pregabalin is a new generation of neuralgia treatment drugs, calcium channel regulators. By regulating o...

Examples

preparation example Construction

[0080] Preparation of pregabalin raw material:

[0081] The pregabalin raw material was prepared according to the method of Example 4 (paragraph [0298] to paragraph [0345]) in CN101848905A (Chinese Patent Application No. 200880107269.2). After determination, its content is 99.2% (HPLC), measured by powder X-ray diffraction, in the powder X-ray diffraction pattern expressed in 2θ angle, there is no diffraction at 9.50°, about 19.04°, about 35.58°, about 38.64° peak.

Embodiment 1

[0082] Embodiment 1: preparation pregabalin crystal

[0083] Add 1 g of the pregabalin raw material prepared according to the method of Example 4 in CN101848905A to the mixed solution of 100ml isopropanol and 40ml acetonitrile, heat to about 50°C to dissolve, add 1.0ml glacial acetic acid to the mixed solution, Stir evenly, slowly cool to about 5°C (stand at this temperature for about 8 hours) to precipitate precipitates, filter the precipitates, wash with isopropanol, and dry in vacuo at 40°C, the yield is 96.3%.

[0084] Determine the content and impurities according to the above-mentioned determination method and related substance detection method respectively.

[0085] The content is 99.6% (HPLC), of which the total impurity is 0.182%, and the largest single impurity is 0.026%.

[0086] Determination of powder X-ray diffraction, the results are as follows figure 1 .

[0087] Powder X-ray diffraction results show that in the powder X-ray diffraction pattern represented...

Embodiment 2

[0093] Embodiment 2: preparation pregabalin crystal

[0094] Add 1 g of the pregabalin raw material prepared according to the method of Example 4 in CN101848905A to the mixed solution of 100ml isopropanol and 35ml acetonitrile, heat to about 50°C to dissolve, add 1.35ml glacial acetic acid to the mixed solution, Stir evenly, slowly cool to about 5°C (stand at this temperature for about 8 hours) to precipitate precipitates, filter the precipitates, wash with isopropanol, and dry in vacuo at 40°C, the yield is 95.4%.

[0095] The content is 99.7% (HPLC), of which the total impurity is 0.173%, and the largest single impurity is 0.014%.

[0096] Determination of powder X-ray diffraction, the results are basically the same as figure 1 Consistent with Table 1, specifically: basically consistent with the 2θ values ​​of the 19 peaks in Table 1, the difference between the 2θ values ​​of each peak and the corresponding peaks in Table 1 is within the range of ±0.10°, and the differenc...

technical field

[0001] The present invention relates to aminomethylhexanoic acid derivatives, especially (S)-3-(aminomethylhexanoic acid derivatives, which can be used for auxiliary treatment of generalized anxiety disorder, diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia syndrome and epilepsy )-A new crystal form of 5-methylhexanoic acid. Background technique

[0002] (S)-3-(aminomethyl)-5-methylhexanoic acid, commonly known as pregabalin, its molecular formula is C 8 h 17 NO 2 , the molecular weight is 159.23. Like gabapentin, pregabalin is a 3-substituted analog of gamma-aminobutyric acid (GABA), and their chemical structures are as follows:

[0003]

[0004] Pregabalin (pregabalin, trade name Lyrica, Lyrica) developed by Pfizer is a 3-position substituted analogue of γ-aminobutyric acid. ) related compounds and their intended successors. Pregabalin is a new generation of neuralgia treatment drugs, calcium channel regulators. By regulating o...

Examples

preparation example Construction

[0080] Preparation of pregabalin raw material:

[0081] The pregabalin raw material was prepared according to the method of Example 4 (paragraph [0298] to paragraph [0345]) in CN101848905A (Chinese Patent Application No. 200880107269.2). After determination, its content is 99.2% (HPLC), measured by powder X-ray diffraction, in the powder X-ray diffraction pattern expressed in 2θ angle, there is no diffraction at 9.50°, about 19.04°, about 35.58°, about 38.64° peak.

Embodiment 1

[0082] Embodiment 1: preparation pregabalin crystal

[0083] Add 1 g of the pregabalin raw material prepared according to the method of Example 4 in CN101848905A to the mixed solution of 100ml isopropanol and 40ml acetonitrile, heat to about 50°C to dissolve, add 1.0ml glacial acetic acid to the mixed solution, Stir evenly, slowly cool to about 5°C (stand at this temperature for about 8 hours) to precipitate precipitates, filter the precipitates, wash with isopropanol, and dry in vacuo at 40°C, the yield is 96.3%.

[0084] Determine the content and impurities according to the above-mentioned determination method and related substance detection method respectively.

[0085] The content is 99.6% (HPLC), of which the total impurity is 0.182%, and the largest single impurity is 0.026%.

[0086] Determination of powder X-ray diffraction, the results are as follows figure 1 .

[0087] Powder X-ray diffraction results show that in the powder X-ray diffraction pattern represented...

Embodiment 2

[0093] Embodiment 2: preparation pregabalin crystal

[0094] Add 1 g of the pregabalin raw material prepared according to the method of Example 4 in CN101848905A to the mixed solution of 100ml isopropanol and 35ml acetonitrile, heat to about 50°C to dissolve, add 1.35ml glacial acetic acid to the mixed solution, Stir evenly, slowly cool to about 5°C (stand at this temperature for about 8 hours) to precipitate precipitates, filter the precipitates, wash with isopropanol, and dry in vacuo at 40°C, the yield is 95.4%.

[0095] The content is 99.7% (HPLC), of which the total impurity is 0.173%, and the largest single impurity is 0.014%.

[0096] Determination of powder X-ray diffraction, the results are basically the same as figure 1 Consistent with Table 1, specifically: basically consistent with the 2θ values ​​of the 19 peaks in Table 1, the difference between the 2θ values ​​of each peak and the corresponding peaks in Table 1 is within the range of ±0.10°, and the differenc...

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