Preparation method of lacidipine impurity B

A technique for lacidipine and impurity, applied in the field of preparation of lacidipine impurity B, can solve problems such as difficulty in applicable industrial production, high catalyst price, difficulty in obtaining impurity B, etc., reduced time to reach, short reaction time, and product impurity little effect

Active Publication Date: 2021-03-09
广州隽沐生物科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Wherein the preparation of impurity B usually exists at the same time of multiple impurities, it is difficult to obtain a single impurity B, and the conversion rate is low. For preparation, it takes about 12 hours at room temperature to convert into the corresponding aromatized product by introducing air and irradiating with visible light. This method uses non-metal as catalyst and oxygen as oxidant. Although the conversion rate is high, but The reaction rate is slow, and a silica gel column is required to separate and purify a special catalyst, which has certain limitations in actual industrial production. There is also the use of nickel as a catalyst for preparation. Lacidipine is dissolved in an acidic aqueous solution, and nickel is used as a catalyst. Catalyst, under the oxidation of oxygen, the lacidipine impurity B can be obtained at room temperature for about 6 hours. This method has a high conversion rate and few by-products, but the catalyst is expensive and difficult to apply to industrial production
[0004] Therefore, for the above-mentioned related technologies, the inventors believe that the cost of preparing lacidipine impurity B is high and the reaction speed is slow, which needs to be further improved

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  • Preparation method of lacidipine impurity B
  • Preparation method of lacidipine impurity B
  • Preparation method of lacidipine impurity B

Examples

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Embodiment 1

[0042] This embodiment discloses a preparation method of lacidipine impurity B, comprising the following steps:

[0043] Step 1), weigh 2 g of lacidipine in an eggplant-shaped bottle, add 30 mL of dichloromethane and stir until dissolved with a glass rod to obtain a preparatory solution;

[0044] Step 2), add 3gDDQ to the eggplant-shaped bottle at a speed of 1.0g / min, slowly add DDQ to the preparatory solution, stir with a magnetic stirrer at a stirring speed of 250rpm, filter after stirring at room temperature for 10 minutes, and obtain the organic Phase is lacidipine impurity B solution;

[0045] Step 3), add 60mL of 5% sodium bicarbonate aqueous solution to the eggplant-shaped bottle that lacidipine impurity B solution is housed, rinse lacidipine impurity B solution, then add 60mL saturated sodium chloride aqueous solution to rinse, then by placing Spin dry in rotary evaporator, obtain the lacidipine impurity B crude product that is yellow solid;

Embodiment 2

[0047] This embodiment discloses a preparation method of lacidipine impurity B, comprising the following steps:

[0048] Step 1), weigh 10 g of lacidipine in an eggplant-shaped bottle, add 50 mL of acetone and stir until dissolved with a glass rod to obtain a preparatory solution;

[0049] Step 2), add 6gDDQ to the eggplant-shaped bottle at a speed of 1.8g / min, slowly add DDQ to the preparatory solution, stir with a magnetic stirrer at a stirring speed of 300rpm, and filter after stirring for 12 minutes at 20°C to obtain The organic phase is lacidipine impurity B solution;

[0050] Step 3), add 100mL of 15% sodium bicarbonate aqueous solution to the eggplant-shaped bottle that lacidipine impurity B solution is housed, rinse lacidipine impurity B solution, then add 100mL saturated sodium chloride aqueous solution to rinse, then by placing Spin dry in rotary evaporator, obtain the lacidipine impurity B crude product that is yellow solid;

[0051] Step 4), add 20mL of absolute et...

Embodiment 3

[0053] This embodiment discloses a preparation method of lacidipine impurity B, comprising the following steps:

[0054] Step 1), weigh 20g of lacidipine into an eggplant-shaped bottle, add 60mL of dichloromethane, and ultrasonically dissolve for 1 minute to obtain a preparatory solution;

[0055] Step 2), add 30gDDQ to the eggplant-shaped bottle at a speed of 2.2g / min, slowly add DDQ to the preparatory solution, stir with a magnetic stirrer at a stirring speed of 350rpm, and filter after stirring for 13 minutes at 50°C to obtain The organic phase is lacidipine impurity B solution;

[0056] Step 3), add 80mL of 20% sodium bicarbonate aqueous solution to the eggplant-shaped bottle that lacidipine impurity B solution is housed, rinse lacidipine impurity B solution, then add 80mL saturated sodium chloride aqueous solution to rinse, then by placing Spin dry in rotary evaporator, obtain the lacidipine impurity B crude product that is yellow solid;

[0057] Step 4), add 30mL of ab...

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Abstract

The invention relates to the technical field of pharmacy, and particularly discloses a preparation method of a lacidipine impurity B. The preparation method comprises the following steps: step 1), adding lacidipine into a solvent, and stirring until lacidipine is dissolved to obtain a prepared solution; step 2) slowly adding DDQ into the prepared solution at the speed of 1.0-3.0 g/min, stirring for more than 10 minutes at the stirring speed of 250-350 rpm at the temperature of 0-50 DEG C, and then filtering to obtain an organic phase, namely a lacidipine impurity B solution, wherein the molarratio of lacidipine to DDQ is 1: 1-3; and step 3) washing the lacidipine impurity B solution with a weak base aqueous solution, washing with a saturated sodium chloride aqueous solution, and spin-drying to obtain the yellow solid lacidipine impurity B. The method has the characteristics of short reaction time, simple preparation process and suitability for industrial production, and the prepared lacidipine impurity B has the advantages of high purity and good properties.

Description

technical field [0001] The application relates to the technical field of pharmacy, more specifically, it relates to a preparation method of lacidipine impurity B. Background technique [0002] Lacidipine is a lipophilic dihydropyridine calcium antagonist, commonly used in the treatment of hypertension and atherosclerosis, and has good antioxidant and vascular selectivity. Currently, lacidipine is in the form of tablets Sold around the world, it is an effective and well-tolerated drug. However, during the production process of the drug, a variety of lacidipine impurities will be produced, which are recorded as lacidipine impurity A in the European Pharmacopoeia. Cidipine impurity B, lacidipine impurity C, in the drug control testing standards, a separate control test for impurity A and impurity B is required to analyze and identify the drug quality of lacidipine. [0003] Wherein the preparation of impurity B usually exists at the same time of multiple impurities, it is diff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/80C07D213/807
CPCC07D213/80C07D213/807
Inventor 赵海龙赖金强陈敏纯张洁枝区沛明肖亮婷徐楷易嘉辉邹小燕周仁学
Owner 广州隽沐生物科技股份有限公司
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