(R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole with stabile physical and chemical properties

A technology of trifluoroethoxy and physicochemical properties, applied in the field of medicine, can solve the problems of crystal appearance and color not conforming to the regulations, unstable placement at room temperature, etc.

Inactive Publication Date: 2014-12-03
SICHUAN HAISCO PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The current dexlansoprazole, in its crystallization process, often has the problems of crystal appearance and color not in compliance with regulations, and unstable storage at room temperature, which are important hidden dangers of drug safety.

Method used

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  • (R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole with stabile physical and chemical properties
  • (R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole with stabile physical and chemical properties
  • (R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole with stabile physical and chemical properties

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole (ie Dexlansoprazole, 100g, 0.27mol), was dissolved in methyl isobutyl ketone (400ml) at about 60°C, and the solution was stirred at 25°C for 6 hours. The precipitated crystals were separated, washed with methyl isobutyl ketone-heptane (methyl isobutyl ketone: heptane = 1:5, 100ml), and dried to obtain the target compound (65g, yield 65%). The appearance of the product is white. The obtained compound (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole The powder X-ray diffraction pattern of the crystal is attached figure 1 . The melting onset temperature of the crystals was 137°C.

Embodiment 2

[0022] (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole (100g , 0.27mol), dissolved in methyl isobutyl ketone (2000ml), and concentrated under reduced pressure to 400ml at an external temperature of about 60°C. Stir at about 25°C for about 5 hours. The precipitated crystals were separated and dried to obtain the target compound (73 g, yield 73%), and the appearance of the product was white. The melting onset temperature of the crystals was 137°C.

Embodiment 3

[0024] (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole (100g , 0.27mol), dissolved in methyl isobutyl ketone (400ml) at about 60°C. The mixture was stirred in methyl isobutyl ketone for about 5 hours, and after precipitation of crystals was confirmed, hexane (2000 ml) was added dropwise over about 15 minutes. The precipitated crystals were separated, washed with methyl isobutyl ketone-hexane (methyl isobutyl ketone: hexane = 1:5, 100ml), and dried to obtain the target compound (93g, yield 93%), product appearance for white. The melting onset temperature of the crystals was 136°C.

[0025] Embodiments 4 to 44 are implemented with reference to the method in Embodiment 3 or the patent document CN1478086.

[0026] See Table 1 below for the products of each example and the stability data for one month at 40°C.

[0027] Table 1 Dexlansoprazole embodiment product and stability data

[0028]

[0029]

[0030]

[0031] Through the i...

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Abstract

The invention belongs to the technical field of medicines, mainly relates to a (R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole compound with stabile physical and chemical properties, and relates to an optically active sulfoxide compound with anti ulcer effect and a preparation method thereof, and by the embodiment of the invention, the stability is greatly improved, compared with compounds obtained by methoda in the prior art, the (R)-2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridyl) methyl] sulfinyl]-1 H-benzimidazole compound has especially good preservation of stability and physical properties. The compounds obtained the crystal preparation method shows excellent anti ulcer activity, gastric acid secretion inhibition effect, mucosal protective effect, anti-helicobacter pylori effect and the like.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy) which is suitable for industrial production and has stable physical and chemical properties. -2-pyridyl]methyl]sulfinyl]-1H-benzimidazole. Background technique [0002] (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H- Benzimidazole is dexlansoprazole, CAS: 138530-94-6. Dexlansoprazole, originally developed by Takeda, is white or off-white in appearance. [0003] Patent document CN1478086 provides the crystallization method of dexlansoprazole: a kind of preparation (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2- Pyridyl]methyl]sulfinyl]-1H-benzimidazole or (S)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2pyridyl A method for ]methyl]sulfinyl]-1H-benzimidazole crystals comprising, at a temperature of about 0°C to about 35°C, from (R)-2- [[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12A61P1/04A61P31/04
CPCC07D401/12
Inventor 汪东海万华冯卫李杰林凡程王海平
Owner SICHUAN HAISCO PHARMA CO LTD
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