Post-treatment method for preparing sitagliptin by using enzyme method and sitagliptin free alkali

A technology of enzymatic preparation and free alkali, applied in the direction of organic chemistry, can solve the problems of low purity of sitagliptin solution, lack of better post-treatment methods, undisclosed post-treatment procedures, etc., and facilitate commercial production and sales, low cost, and easy storage and transportation

Inactive Publication Date: 2021-03-05
ZHEJIANG YONGTAI CHIRAL MEDICINE TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The patent does not disclose the post-treatment process, and the directly obtained sitagliptin solution is not of high purity, which is inconvenient for storage and transportation. The prior art does not provide a better post-treatment method

Method used

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  • Post-treatment method for preparing sitagliptin by using enzyme method and sitagliptin free alkali
  • Post-treatment method for preparing sitagliptin by using enzyme method and sitagliptin free alkali
  • Post-treatment method for preparing sitagliptin by using enzyme method and sitagliptin free alkali

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] (1) Add 6mM HCl to the reaction solution for preparing sitagliptin by enzymatic method to adjust the pH to 1-2 to terminate the reaction, add diatomaceous earth and suction filter to remove the enzyme, and extract the filtrate twice with dichloromethane to remove impurities and unreacted raw materials .

[0052] (2) Use liquid caustic soda to adjust the pH to 7, distill under reduced pressure, steam out 20% of water, and remove dichloromethane dissolved in water.

[0053] (3) Cool down to room temperature, adjust the pH to 12 with liquid caustic soda, stir for 16 hours, and after the viscous material is solidified and dispersed, filter with suction and dry at 60° C. for 4 hours to obtain 14.66 g of sitagliptin free base, with a yield of 72%. , 99.5% purity.

Embodiment 2

[0055] (1) Add 6mM HCl to the reaction solution for preparing sitagliptin by enzymatic method to adjust the pH to 1-2 to terminate the reaction, add diatomaceous earth and suction filter to remove the enzyme, and extract the filtrate twice with dichloromethane to remove impurities and unreacted raw materials .

[0056] (2) Use liquid caustic soda to adjust the pH to 7, and perform long-pressure distillation to steam out 30% of water, and remove the dichloromethane dissolved in water.

[0057] (3) Cool down to room temperature, adjust the pH to 12 with liquid caustic soda, stir for 8 hours, and after the viscous material is solidified and dispersed, filter with suction and dry at 70°C for 8 hours to obtain 16.08 g of sitagliptin free base, with a yield of 79%. , 99.6% purity.

Embodiment 3

[0059] (1) Add 6mM HCl to the reaction solution for preparing sitagliptin by enzymatic method to adjust the pH to 1-2 to terminate the reaction, add diatomaceous earth and suction filter to remove the enzyme, and extract the filtrate twice with dichloromethane to remove impurities and unreacted raw materials .

[0060] (2) Use liquid caustic soda to adjust the pH to 7, distill under reduced pressure, steam out 40% of water, and remove dichloromethane dissolved in water.

[0061] (3) Cool down to room temperature, adjust the pH to 12 with liquid caustic soda, stir for 4 hours, and after the viscous material is solidified and dispersed, filter with suction and dry at 60° C. for 4 hours to obtain 17.29 g of sitagliptin free base, with a yield of 85%. , 99.9% purity.

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Abstract

The invention discloses a post-treatment method for preparing sitagliptin by an enzymic method and sitagliptin free alkali, belonging to the technical field of chemical pharmacy. The method comprisesthe following steps: acidifying a reaction solution for preparing sitagliptin via the enzyme method, and removing enzymes, impurities and unreacted raw materials; adjusting the pH value of a residualreaction solution to 5-9, evaporating out water, and removing an organic solvent dissolved in water; conducting cooling, adjusting the pH value of the residual reaction solution to 11-13 so as to realize material solidification and dispersion, performing suction filtration, and then conducting drying to obtain the sitagliptin free alkali. The method is high in stability, simple to operate and lowin cost, high-purity and high-yield sitagliptin free alkali solid powder can be obtained, wastewater treatment is facilitated, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of chemical industry and pharmaceuticals, in particular to a post-treatment method for enzymatically preparing sitagliptin and sitagliptin free base. Background technique [0002] Sitagliptin phosphate (Sitagliptin phosphate) is the first dipeptidyl peptidase (DPP-IV) inhibitor developed by Merck Company of the United States in October 2006 approved by the FDA. At the third annual meeting of the Diabetes Society of the Chinese Medical Association, the State Food and Drug Administration has officially approved the trade name Januvia to be launched in China. Sitagliptin phosphate is mainly used for the treatment of type II diabetes. It has obvious hypoglycemic effect when used alone or in combination with metformin and biglitazone. It is safe to take, well tolerated, and has few adverse reactions. Sitagliptin phosphate has always been one of the hot drugs for treating type II diabetes, and it is currently com...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 夏海建张峰覃晓
Owner ZHEJIANG YONGTAI CHIRAL MEDICINE TECH CO LTD
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