Novel method for preparing high-purity asthma treatment drug pranlukast

The technology of an asthma drug and a new method, which is applied in the field of drug organic synthesis, can solve the problems of cumbersome operation, high cost, low content of crude prankast, and achieves the effect of simple process and easy control.

Active Publication Date: 2017-06-16
ANHUI HERYI CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] 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 is always in strong alkali, the resulting pullen is obtained under the condition of strong alkali closed loop. The content of the crude product of Siter is very low, and multiple purifications are required 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 continue the reaction. 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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  • Novel method for preparing high-purity asthma treatment drug pranlukast

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Experimental program
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Effect test

Embodiment 1

[0022] Dissolve 80g of 8-amino-4-oxo-2-tetrazol-5-yl-4H-1benzopyran hydrochloride in 500ml of dichloromethane, add 65g of triethylamine dropwise, and reflux after the dropwise reaction 2h, recover dichloromethane, stir the residue at 0°C for 30min, and filter with suction to obtain the intermediate 8-amino-4-oxo-2-pyrazol-5-yl-4H-1-benzopyran mono Triethylamine salt 93g.

[0023] 8-amino-4-oxo-2-backazol-5-yl-4H-1-benzopyran monotriethylamine salt 67g, p-phenylbutoxybenzoyl chloride 60g drop into a container containing 700ml dichloromethane In a 1000ml reaction bottle, stir and heat up to reflux for 6 hours, recover dichloromethane, add 1200ml of 5% alkaline water to the residue, stir, add a little activated carbon for decolorization, freeze and crystallize to obtain prankast sodium salt, and then dissolve the obtained prankast sodium salt Add ster sodium salt into 500ml of ethanol, add 500ml of water, adjust the pH to 6.8-7.2 with hydrochloric acid under stirring, after rete...

Embodiment 2

[0025] Dissolve 80 g of 8-amino-4-oxo-2-tetrazol-5-yl-4H-1 benzopyran hydrochloride in 500 ml of dichloromethane, add 50 g of pyridine dropwise, and reflux for 2 hours after the drop is complete. Recover dichloromethane, stir the residue at 0°C for 30 minutes, and filter with suction to obtain the intermediate 8-amino-4-oxo-2-pyrazol-5-yl-4H-1-benzopyran monopyridinium salt 86g.

[0026] Put 62g of 8-amino-4-oxo-2-backazol-5-yl-4H-1-benzopyran monopyridinium salt and 60g of p-phenylbutoxybenzoyl chloride into 1000ml of 700ml of dichloromethane for reaction In the bottle, after stirring and raising the temperature to reflux for 6 hours, reclaim dichloromethane, add 1200ml of 5% alkaline water to the residue, stir, add a little activated carbon for decolorization, freeze and crystallize to obtain prankast sodium salt, and then dissolve the obtained prankast Put the sodium salt into 500ml of ethanol, add 500ml of water, adjust the pH to 6.8-7.2 with hydrochloric acid under stirr...

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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

[0001] Technical field: [0002] The invention relates to the technical field of organic synthesis of medicines, in particular to a new method for preparing high-purity asthma drug prankast. [0003] Background technique: [0004] Pranlukast is developed by Japan Ono Company, it only selectively inhibits leukotriene receptors, has almost no effect on arachidonic acid metabolizing enzymes, and has no antagonistic effect on acetylcholine, 5-hydroxytryptamine, etc. Both atopic asthma and other types of bronchial asthma have good therapeutic effects. [0005] At present, there are two main methods for the commercial production of pranlukast commonly used at home and abroad: the first method is to use 3′-(4-(4-phenylbutoxy)benzoic acid amine)-2′-hydroxybenzene Ethyl ketone (PBHA) is raw material, and in polar solvent, in the presence of strong base, ester ketone condensation reaction occurs with ethyl tetrachlorazole formate, then ring-closing under acidic conditions generates pran...

Claims

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Application Information

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Patent Type & Authority Applications(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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