Chemical resolution preparation method of S-configuration pregabalin

A pregabalin and chemical separation technology, applied in the S-configuration pregabalin separation process and compound preparation field, to achieve the effects of less environmental pollution, high optical purity and low production cost

Inactive Publication Date: 2014-03-12
河北爱弗特精细化工有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The main purpose of the present invention is to split the existing R / S-pregabalin racemate to obtain the problems and deficiencies in the S-pregabalin method, and provide A new chemical resolution method

Method used

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  • Chemical resolution preparation method of S-configuration pregabalin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] (1) Salt forming process

[0023] In a 50mL clean three-neck flask, add 5.50g of p-toluenesulfonamido-D-phenylglycine and 40mL of isopropanol solution with a volume ratio of 3%, and heat to dissolve; add 2.40g of pregabalin racemate, and keep warm at a slow speed Stir for 0.5h, cool down naturally at 30-35°C, and crystallize for 4h. Suction filtration, transfer the obtained solid to 15 mL of isopropanol solution with a volume ratio of 3%, keep stirring at 50°C for 1h, cool to 30°C, crystallize for 1h, suction filtration, and dry to obtain 3.0g of S-pregabalin and p- Methylbenzenesulfonamide-D-phenylglycinate complex.

[0024] (2), depolymerization process

[0025] Suspend 3.0 g of the above-mentioned salt complex in 15 mL of deionized water, adjust pH = 0.5-1 with 10% hydrochloric acid, stir at room temperature for 3 h, filter, wash with 4 mL of water, dry, and recover the resolving agent p-toluenesulfonamide -D-phenylglycine 2.0 g. Adjust the pH = 6 to 6.5 with 20%...

Embodiment 2

[0027] (1) Salt forming process

[0028] In a 100mL clean three-necked flask, add 5.0g of benzenesulfonamide-D-phenylglycine and 40mL of 3% isopropanol solution by volume, heat to dissolve; add 2.40g of pregabalin racemate, keep warm and stir slowly for 0.5h , natural cooling 30 ~ 35 ℃, crystallization 6h. Suction filtration, the obtained solid was transferred to 30 mL of isopropanol solution with a volume ratio of 3%, kept stirring at 50°C for 2h, cooled to 30°C, crystallized for 3h, suction filtration, and dried to obtain 2.80g of S-pregabalin and benzene Sulfonamide-D-phenylglycinate complex.

[0029] (2), depolymerization process

[0030]Suspend 2.80 g of the above salt complex in 15 mL of deionized water, adjust pH = 0.5-1 with 10% hydrochloric acid, stir at room temperature for 3 h, filter, wash with 5 mL of water, dry, and recover the resolving agent benzenesulfonamide group-D- Phenylglycine 1.8g. Use 10% sodium hydroxide to adjust pH = 6 to 6.5. Concentrate 8 mL o...

Embodiment 3

[0032] (1) Salt forming process

[0033] In a 50mL clean three-neck flask, add 5.50g of p-toluenesulfonamido-D-phenylglycine and 45mL of isopropanol solution with a volume ratio of 3%, and heat to dissolve; add 2.40g of pregabalin racemate, and keep warm at a slow speed Stir for 0.5h, cool down naturally at 30-35°C, and crystallize for 6h. Suction filtration, the obtained solid was transferred to 15 mL of isopropanol solution with a volume ratio of 3%, kept stirring at 50°C for 2h, cooled to 30°C, crystallized for 2h, suction filtration, and drying to obtain 3.10g of S-pregabalin and para Methylbenzenesulfonamide-D-phenylglycinate complex.

[0034] (2), depolymerization process

[0035] Dissolve 3.10 g of the above-mentioned salt complex in 20 mL of 50% methanol solution by volume, adjust the pH = 6.5-7 with ammonia water, stir at room temperature for 3 h, cool down to 0 ° C, keep warm overnight, filter, wash with 2 mL of cold water, and dry to obtain White S-pregabalin 0.7...

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Abstract

The invention provides a method for preparing S-configuration pregabalin by resolving a pregabalin racemate. The method comprises the following steps: by taking toluenesulfonamide-D-phenylglycine or benzenesulfonamido-D-phenylglycine as a resolving agent, resolving in a water-borne alcoholic solution; and fully washing by using a resolving solvent, thus obtaining a compound of S-pregabalin and toluenesulfonamide-D-phenylglycine or benzenesulfonamido-D-phenylglycine; performing depolymerization in an aqueous solution or an alcoholic solution, thus obtaining the S-configuration pregabalin. The technical method provided by the invention is simple to operate and high in resolution efficiency, hardly causes environmental pollution and is suitable for industrial production, and the resolving agent and the resolving solvent are easy to recycle.

Description

technical field [0001] The invention relates to the technical field of compound preparation, in particular to the technical field of S-configuration pregabalin resolution technology, in particular to the chemical resolution preparation method of S-configuration pregabalin. Background of the invention [0002] The chemical name of Pregabalin is (S)-3-aminomethyl-5-methylhexanoic acid, which is a new type of γ-aminobutyric acid (GABA) receptor agonist developed by Pfizer. It was first approved by the European Union in 2004 under the trade name Lyrica for the treatment of partial seizures in adult patients. It was launched in the United States in 2006, adding new indications for the treatment of generalized anxiety disorder and social anxiety disorder. In 2009, it was approved for the treatment of spinal cord injury, trauma, multiple sclerosis, diabetic nerve pain and band Herpetic nerve pain is currently widely used clinically and has become one of the best-selling drugs in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C227/34C07C229/08
Inventor 付德才张伟王博石少龙谷明明郑美玲单国申张中文
Owner 河北爱弗特精细化工有限责任公司
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