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Preparation process of high-purity palonosetron Hcl

A technology of palonosetron and preparation process, which is applied in the field of organic synthesis, can solve the problems of difficult product quality, multiple impurities and the like, achieves the effects of quality controllability and product quality improvement

Active Publication Date: 2008-12-03
NANJING SIMCERE DONGYUAN PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the synthesis process disclosed in U.S. Patent No. 5,510,486, the obtained crude palonosetron hydrochloride is recrystallized once with isopropanol to remove impurities, but after the crude product is recrystallized by this method, there are still more impurities in the product. Moreover, the purity of the finished product can only reach 99% after multiple recrystallizations, and the content of a single impurity exceeds 0.1%. It is very difficult to further improve the quality of the product

Method used

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  • Preparation process of high-purity palonosetron Hcl
  • Preparation process of high-purity palonosetron Hcl
  • Preparation process of high-purity palonosetron Hcl

Examples

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Effect test

Embodiment 2

[0040] Example 2 New Method 2 Preparation of Palonosetron Hydrochloride

[0041]Weigh 20.0 g of the pre-column crude product of palonosetron hydrochloride prepared in Example 1, and perform elution according to the elution conditions of Example 1 to prepare 10.0 g of crude product of palonosetron hydrochloride. Dissolve the crude palonosetron hydrochloride in 250mL of chloroform, then add 0.1g of activated carbon, stir at room temperature for 30 minutes, filter and concentrate to dryness, then add 200mL of 95% ethanol, heat to dissolve completely, and then concentrate to dryness under reduced pressure; add 60mL Dissolve in water, pass through a 0.22μm microporous membrane, filter out a small amount of insoluble matter, concentrate the mother liquor under reduced pressure; add 230mL of isopropanol and 9mL of water, heat to dissolve all the solids, then continue to heat, and distill at normal pressure until 70mL of liquid is evaporated Afterwards, the distillation was stopped, c...

Embodiment 3

[0042] Example 3 New Method 3 Preparation of Palonosetron Hydrochloride

[0043] Weigh 20.0 g of the pre-column crude product of palonosetron hydrochloride prepared in Example 1, and perform elution according to the elution conditions of Example 1 to prepare 10.3 g of crude product of palonosetron hydrochloride. Add 250mL of 80% ethanol, heat to dissolve completely, then concentrate to dryness under reduced pressure; then add 100mL of water to dissolve, pass through a 0.8μm microporous membrane, filter out a small amount of insoluble matter, concentrate the mother liquor under reduced pressure, and finally add 45mL×2 anhydrous Add 200 mL of absolute ethanol, heat to dissolve all the solids, cool to room temperature, crystallize in an ice bath for 2 hours, filter, and dry the precipitate under reduced pressure to obtain 9.2 g of the finished product. The purity of the product is 99.82% through HPLC detection, and the single impurity is below 0.05%; through gas phase detection, ...

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Abstract

The invention relates to a novel preparation method of high-purity (3aS)-2-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-2,3,3aS,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one Hydrochloride (namely, Palonosetron hydrochloride) which comprises the three steps as follows: (1) separating the Palonosetron hydrochloride by silica gel column chromatography to obtain Palonosetron hydrochloride coarse product, dissolving in ethanol, concentrating and drying; (2) dissolving in water, filtering to remove water-insoluble impurities, concentrating, and drying; and (3) re-crystallizing.

Description

technical field [0001] The present invention relates to the field of organic synthesis, more specifically, to a high-purity 2-[(3S)-1-azabicyclo[2.2.2]octyl]-2,3,3aS,4,5,6 - A new preparation process of hexahydro-1H-benzo[de]isoquinolin-1-one hydrochloride (ie palonosetron hydrochloride). Background of the invention [0002] Palonosetron Hydrochloride (Palonosetron Hydrochloride, trade name: Xileduo, Aloxi) is a selective 5-HT3 receptor antagonist developed by Helsinn Company in Switzerland, and its chemical name is: 2-[(3S)-1-azabicyclo [2.2.2] Octyl]-2,3,3aS, 4,5,6-hexahydro-1H-benzo[de]isoquinolin-1-one hydrochloride, molecular structure formula (see I). It was approved by the US Food and Drug Administration (FDA) on July 25, 2003, for the prevention of acute and delayed nausea and vomiting induced by moderately or highly emetogenic chemotherapy. [0003] [0004] Palonosetron hydrochloride is the fourth approved 5-HT3 receptor antagonist. Its important feature is i...

Claims

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Application Information

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IPC IPC(8): C07D453/02A61P1/08
Inventor 张连第郭仁平张斐丁磊
Owner NANJING SIMCERE DONGYUAN PHARM CO LTD
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