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A new method for preparing high-purity asthma medicine pranlukast

An asthma drug and a new method technology, applied in the field of organic drug synthesis, can solve the problems of cumbersome operation, high cost, and low content of pranlukast crude product, and achieve the effect of simple process and easy control

Active Publication Date: 2020-11-13
ANHUI HERYI CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The first method requires the use of a large amount of polar solvents and a large amount of strong alkali that are difficult to recycle and apply mechanically. The production process produces a large amount of waste liquid, waste residue and waste water, and because the material has been in strong alkali, the closed-loop condition of strong alkali leads to the obtained pullen The content of the crude product of Siter is very low, and it needs multiple purifications to reach more than 99.5%. The second method has the same problem as the above method. Because AOTH contains hydrochloric acid, it is necessary to neutralize the hydrochloric acid with an acid-binding agent in the reaction process to free the amino group. The hydrogen chloride produced in the reaction process still needs to be removed in time to make the reaction continue. The purity of the crude product is only 80-85%. Not only does it need multiple purifications, but the operation is cumbersome and the cost is very high. high

Method used

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  • A new method for preparing high-purity asthma medicine pranlukast

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Experimental program
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Effect test

Embodiment 1

[0018] Dissolve 80 g of 8-amino-4-oxo-2-tetrazol-5-yl-4H-1 benzopyran hydrochloride in 500 ml of dichloromethane, add 65 g of triethylamine dropwise, and reflux for reaction after dropping After 2h, the dichloromethane was recovered, the residue was stirred at 0℃ for 30min, and then filtered with suction to obtain the intermediate 8-amino-4-oxo-2-oxazol-5-yl-4H-1-benzopyran Triethylamine salt 93g.

[0019] 67g of 8-amino-4-oxo-2-oxazol-5-yl-4H-1-benzopyran monotriethylamine salt and 60g of p-phenylbutoxybenzoyl chloride were put into a 700ml dichloromethane After stirring and refluxing for 6 hours in a 1000ml reaction flask, dichloromethane was recovered, 1200ml of 5% alkaline water was added to the remainder, stirred, and a little activated carbon was added for decolorization, freezing and crystallization to obtain Pranlukast sodium salt, and then the obtained Pranlukast Ster sodium salt was put into 500ml ethanol, 500ml water was added, and the pH was adjusted to 6.8-7.2 with ...

Embodiment 2

[0021] 80g of 8-amino-4-oxo-2-tetrazol-5-yl-4H-1 benzopyran hydrochloride was dissolved in 500ml of dichloromethane, 50g of pyridine was added dropwise, and the reaction was refluxed for 2h after dropping. The dichloromethane was recovered, and the residue was stirred at 0°C for 30 min, and filtered with suction to obtain the intermediate 8-amino-4-oxo-2-oxazol-5-yl-4H-1-benzopyran monopyridine salt 86g.

[0022] 62g of 8-amino-4-oxo-2-oxazol-5-yl-4H-1-benzopyran monopyridine salt and 60g of p-phenylbutoxybenzoyl chloride were put into 1000ml reaction containing 700ml of dichloromethane After stirring and refluxing for 6 hours, the dichloromethane was recovered, and 1200ml of 5% alkaline water was added to the remainder, stirred, and a little activated carbon was added for decolorization, frozen and crystallized to obtain the sodium salt of Pranlukast. Sodium salt was put into 500ml ethanol, 500ml water was added, pH was adjusted to 6.8-7.2 with hydrochloric acid while stirring,...

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Abstract

The invention discloses a novel method for preparing a high-purity asthma treatment drug pranlukast, and relates to the technical field of organic synthesis of drugs. The method comprises the following steps: carrying out neutralization and a salt forming reaction on a reaction raw material 8-amino-4-oxo-2-tetrazole-5-yl-4H-1-benzopyran hydrochloride and an alkaline substance to generate an intermediate, and carrying out an amidation reaction on the obtained intermediate and p-phenylbutoxybenzoyl chloride in a non-polar solvent to prepare the pranlukast. The whole process of the method is simple and clean, is easy to control, allows the purity of the obtained crude product to reach 99% or above, and allows the purity of a one-time purified product to reach 99.9% or more.

Description

Technical field: [0001] The invention relates to the technical field of drug organic synthesis, in particular to a new method for preparing a high-purity asthma drug Pranlukast. Background technique: [0002] Pranlukast is developed by Japan's Ono Company. It only selectively inhibits leukotriene receptors and has almost no effect on arachidonic acid metabolizing enzymes. At the same time, it has no antagonistic effect on acetylcholine and serotonin. Atopic asthma and other types of bronchial asthma have good therapeutic effects. [0003] At present, there are two main methods of commercial production of Pranlukast commonly used at home and abroad: The first method is 3′-(4-(4-phenylbutoxy)benzoic acid amine)-2′-hydroxybenzene Ethyl ketone (PBHA) is used as the raw material, in the presence of a strong base in a polar solvent, the ester-ketone condensation reaction occurs with ethyl tetrachloroazole formate, and then the ring is closed under acidic conditions to form Pranlukast; t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D407/04
CPCC07D407/04
Inventor 董来山刘忠平何长林王东健
Owner ANHUI HERYI CHEM
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