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A kind of preparation method of praziquantel and its intermediate compound

A compound, the technology of praziquantel, which is applied in the field of preparation of praziquantel, can solve the problems of high price, perishability, low reactivity and selectivity, and achieve high total reaction yield, reasonable process design and cheap raw materials Easy to get effect

Active Publication Date: 2019-07-23
ZHEJIANG HISUN PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But because the raw material halogenated acetaldehyde acetal that it adopts has higher price, lower reactivity and selectivity, and the raw material aminoacetyl halide hydrochloride is poor in stability and perishable, thus it is also unfavorable for industrialized production

Method used

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  • A kind of preparation method of praziquantel and its intermediate compound
  • A kind of preparation method of praziquantel and its intermediate compound
  • A kind of preparation method of praziquantel and its intermediate compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Step 1): Add β-phenylethylamine (15.36g, 126.75mmol), CH 2 Cl 2 (150ml) and NaOH (7.30g, 182.50mmol), add chloroacetyl chloride (15.0g, 132.80mmol) dropwise under cooling in an ice-water bath, and continue the reaction for 1h after the addition is complete. Then add 150ml of water to the reaction solution, stir and let it stand, separate the organic layer, wash the organic phase with 50ml of dilute hydrochloric acid aqueous solution, wash twice with 100ml×2 water, dry over anhydrous magnesium sulfate, filter and concentrate to obtain white The compound of formula II was 24.73 g, and the yield was 98.7%.

[0049] 1 HNMR (CDCl 3 )δ: 2.86 (t, 2H), 3.57 (q, 2H), 4.02 (s, 2H), 6.59 (s, 1H), 7.20-7.35 (m, 5H).

[0050] MS (ESI) m / z: 198.07 ([M+1] + ), 220.05 ([M+Na] + ).

[0051] Step 2): Add the above-prepared compound of formula II (22.90 g, 115.85 mmol) and ethanolamine (42.60 g, 697.45 mmol) sequentially into a 250 ml reaction flask, and stir at room temperature fo...

Embodiment 2

[0064] Except for preparing the compound of formula II in step 1) as follows, other steps are the same as in Example 1.

[0065] Add β-phenylethylamine (15.36g, 126.75mmol), CH 2 Cl 2 (150ml) and NaHCO 3 (21.30g, 253.54mmol), and chloroacetyl chloride (15.0g, 132.80mmol) was added dropwise under cooling in an ice-water bath, and the reaction was continued for 1h after the addition was completed. Then add 150ml of water to the reaction solution, stir and let it stand, separate the organic layer, wash the organic phase with 50ml of dilute hydrochloric acid aqueous solution, wash twice with 100ml×2 water, dry over anhydrous magnesium sulfate, filter and concentrate to obtain white The compound of formula II was 24.85 g, and the yield was 99.2%.

Embodiment 3

[0067] Except for preparing the compound of formula II in step 1) as follows, other steps are the same as in Example 1.

[0068] Add β-phenylethylamine (15.36g, 126.75mmol), CH 2 Cl 2 (150ml) and Na 2 CO 3 (20.15g, 190.11mmol), and chloroacetyl chloride (15.0g, 132.80mmol) was added dropwise under cooling in an ice-water bath, and the reaction was continued for 1h after the addition was completed. Then add 150ml of water to the reaction solution, stir and let it stand, separate the organic layer, wash the organic phase with 50ml of dilute hydrochloric acid aqueous solution, wash twice with 100ml×2 water, dry over anhydrous magnesium sulfate, filter and concentrate to obtain white The compound of formula II was 24.38g, and the yield was 97.3%.

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Abstract

The invention discloses a preparation method of praziquantel and an intermediate thereof. The method uses β-phenylethylamine as a starting material, undergoes successive condensation, substitution and acylation reactions with chloroacetyl chloride, ethanolamine and cyclohexanoyl chloride, and then undergoes oxidation and cyclization reactions to obtain the target product Praziquantel. The invention also discloses two key intermediate compounds of formula IV and formula V for preparing praziquantel. The process design of the method of the invention is reasonable and simple, the reaction conditions are mild, economical and environmentally friendly, the raw materials are cheap and easy to obtain, the key intermediates are easy to prepare, the total reaction yield is high (≥60%), and the obtained target product formula I compound praziquantel The purity is high (purity determined by HPLC≥99.8%), so it is easy to realize large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and relates to a preparation method of an anti-parasitic drug praziquantel and an intermediate thereof, in particular to an improved preparation method of praziquantel and the intermediate shown in formula IV and formula V Compound, as well as the preparation method and use of the intermediate compound. Background technique [0002] Praziquantel is a broad-spectrum antiparasitic drug, suitable for schistosomiasis japonicum, schistosomiasis haematobium, schistosomiasis mansoni, paragonimiasis (paragonimiasis), clonorchiasis, including It is especially suitable for the treatment of schistosomiasis and clonorchiasis. Since Praziquantel was first launched in Germany under the trade name "Cesol" in 1980, it quickly became the drug of choice for the treatment of helminthiasis. Its chemical structure is shown in the following formula I: [0003] [0004] German patents DE 2504250 and DE 2508947 respe...

Claims

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Application Information

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IPC IPC(8): C07D471/04A61K31/4985A61P33/00A61P33/12
CPCA61K31/4985C07D471/04A61P33/00A61P33/02A61P33/10A61P33/12C07C231/02C07C231/14C07C237/22
Inventor 张福利杨哲洲包如胜徐伟伟白骅
Owner ZHEJIANG HISUN PHARMA CO LTD