New preparation method of azilsartan kamedoxomil

A technology for azilsartan medoxomil and potassium salt, applied in the field of preparing azilsartan medoxomil potassium salt, can solve the problems of poor solubility of azilsartan medoxomil, unfavorable for industrialized production, easy to exceed the standard of residue on ignition, etc. The effect of poor solubility, simple operation and high product purity

Inactive Publication Date: 2016-07-13
CHONGQING LAND TOWER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The route is simple. Although the yield is high, the solubility of azilsartan medoxomil is poor, it is basically insoluble in methanol, and the addition of potassium salt is incomplete.
Not conducive to industrial production
In addition, if potassium chloride is used, the residue on ignition will easily exceed the standard

Method used

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  • New preparation method of azilsartan kamedoxomil

Examples

Experimental program
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Effect test

Embodiment 1

[0030] Preparation of the complex: Add 5 g of azilsartan medoxomil and 70 ml of ethyl acetate into a dry reaction bottle. Stir to lower the temperature, and add 1 g of triethylamine dropwise at 10-15°C. Stir to dissolve, and obtain the ethyl acetate solution of azilsartan medoxomil triethylamine salt. This intermediate was directly carried on to the next step without treatment.

[0031] Add dropwise 20ml of ethyl acetate solution of 1.8g potassium isooctanoate to the ethyl acetate clear solution of azilsartan medoxomil triethylamine salt at 10~15°C. After the dropwise addition was completed, stir for 1 h, crystallize, and filter to obtain 5.0 g of azilsartan medoxomil potassium salt with a yield of 94.1% and a purity of 99.6%. mp: 209.4~210.8°C, (literature data: 209~213°C).

[0032] 1 HNMR (DMSO-d6) б1.37-1.41 (3H, t), 2.16 (3H, s), 4.57-4.63 (2H, q), 5.12 (2H, s), 5.55 (2H, s), 6.86-6.88 (2H, d), 7.19-7.46 (4H, m), 7.52-7.54 (2H, m), 7.62-7.63 (2H, m), 1.37-1.41 (3H, m)...

Embodiment 2

[0034] Preparation of the complex: Add 10 g of azilsartan medoxomil and 75 ml of acetone into a dry reaction bottle. Stir to lower the temperature, and add 1.5 g of pyridine dropwise at 15-20°C. Stir to dissolve, and obtain the acetone solution of azilsartan medoxomil pyridinium salt. This intermediate was directly carried on to the next step without treatment.

[0035] At 15~20°C, 20ml of acetone solution containing 3.4g of potassium isooctanoate was added dropwise to the clear solution of azilsartan medoxoproxil pyridinium salt in acetone, after the dropwise addition was completed, stirred for 1 hour, crystallized and filtered to obtain Azilsartan Ester potassium salt 9.96g, yield 93.1%, purity 99.4%. mp: 208.9~210.7°C.

Embodiment 3

[0037] Preparation of the complex: Add 9.5 g of azilsartan medoxomil and 75 ml of acetone into the dry reaction bottle. Stir to lower the temperature, and add 1.8 g of triethylamine dropwise at 12-17°C. Stir to dissolve, and obtain the acetone solution of azilsartan medoxomil triethylamine salt. This intermediate was directly carried on to the next step without treatment.

[0038] Add dropwise 20ml of acetone solution of 3.4g potassium isooctanoate to the acetone clarified solution of azilsartan medoxomil triethylamine salt at 12~17°C. After the dropwise addition was completed, stir for 2 hours, crystallize, and filter to obtain 9.6 g of azilsartan medoxomil potassium salt, with a yield of 95.05% and a purity of 99.7%. mp: 208.4~210.5°C.

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Abstract

The invention discloses a new preparation method of azilsartan kamedoxomil. The preparation method is characterized by comprising the steps: taking azilsartan medoxomil as a raw material, carrying out a reaction with an organic alkali to obtain azilsartan medoxomil organic amine salt with high solubility, and then carrying out a reaction of the azilsartan medoxomil organic amine salt with an organic kali salt to obtain the target product-azilsartan kamedoxomil. Compared with a conventional process, the method has the advantages of novel design, low impurity, high yield and the like. Moreover, the operation is safe and convenient, the problem of poor solubility of azilsartan medoxomil is solved, and the preparation method has industrialized prospect.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a new process for preparing azilsartan medoxomil potassium salt. Background technique [0002] Azilsartan medoxomil potassium salt raw materials and preparations are angiotensin II receptor antagonist drugs for the treatment of hypertension developed by Takeda Pharmaceutical Company Limited. It is mostly used for the treatment of hypertension and is currently the only vascular tension drug in the late clinical stage. Drugs that block hormone II receptors (sartans). It was launched in the United States on February 22, 2011 for the treatment of essential hypertension. Its chemical name is (5-methyl-2-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5- Oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1 H - Benzimidazole-7-carboxylate potassium salt. As shown in structural formula 1: [0003] [0004] The preparation technology of Azilsartan medoxomil pota...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/14
Inventor 陈顺祥孟文学龙道兵
Owner CHONGQING LAND TOWER PHARMA
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