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Crystalline form of pyrrole-type gastric acid secretion inhibitor compound salt and preparation thereof

A technology of pyrrole and crystal form, applied in the field of chemical medicine, can solve the problems of limiting acid suppression and treating gastric acid-related diseases, poor water solubility of compounds, etc., and achieves the effects of good product quality, low preparation cost and low hygroscopicity

Inactive Publication Date: 2017-05-10
JIANGSU CAREFREE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] TAK438 (5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylaminofumarate) is a potassium Ion-competitive acid blocker (P-CAB), in vitro experiments show that the ability of this compound to inhibit proton pump (H+, ATPase) is 400 times that of lansoprazole, which can effectively inhibit gastric acid secretion and has a long-lasting effect advantages, but the compound has poor water solubility, and the oral bioavailability of animals is only 10%, which limits the compound's ability to suppress acid and treat gastric acid-related diseases
[0004] As 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamoacetate, none of the existing literature refers to the crystal form of this compound Preparation, this paper provides a method for preparing the acetate crystal form of the compound. This crystal form has the advantages of good stability, good solubility, and easy production and scale-up, which is very necessary for future industrial production.

Method used

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  • Crystalline form of pyrrole-type gastric acid secretion inhibitor compound salt and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] In a 100 mL one-necked bottle, add 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylamine (3.0 g, 8.7 mmol) and Ethyl acetate (15 mL) was stirred and dissolved at room temperature (15°C), acetic acid (0.6 mL, 9.1 mmol) was added dropwise to the reaction system, stirred at this temperature for 30 minutes, and then the temperature was lowered to 2°C, And stirred for 30 minutes, a solid precipitated, the solid was filtered out, and washed with ethyl acetate (8 mL*2 times), and the obtained solid was dried in a vacuum oven (35°C) for 4 hours to obtain 3.1 g of off-white solid, The yield was 88%.

[0019] Disperse 3.0g of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamate in 50ml of ethyl acetate, stir and heat to 50±5°C, keep stirring for 2h, cool down naturally, filter with suction, and vacuum-dry the filter cake at 35±5°C to obtain 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl) )-1H-pyrrole-3-carbamoacetate crystal form.

Embodiment 2

[0021] 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamoacetate crystal form

[0022] 1. Influencing factor experiment:

[0023] High temperature (40°C) and high temperature (60°C) samples were taken on the 5th and 10th day respectively, the properties of the compound (color, solubility) were studied, and the related substances and contents were detected by high performance liquid chromatography. High humidity (75%RH),

[0024] High humidity (92.5% RH) samples were taken on the 5th and 10th day respectively, and the properties of the compound (color, solubility) were studied, and the relevant substances and contents were detected by high-performance liquid chromatography.

[0025] Illumination (4500 lx) samples were taken on the 5th and 10th days respectively, and the properties of the compounds (color, solubility) were studied, and the relevant substances and contents were detected by high performance liquid chromatography.

[0026] 1. Accelerated test...

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Abstract

The present invention provides a crystalline form of a 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylamine salt compound, the crystalline form is characterized in that in an X-ray powder diffraction spectrum obtained by Cu-K [alpha] radiation and represented by 2 [theta] angle, the crystalline form of the 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylamine salt compound has characteristic diffraction peaks at 9.7, 10.1, 15.2, 17.8, 20.3, 24.9 and 25.8. The crystalline form has good stability and solubility. A preparation method of the crystalline form is also provided.

Description

technical field [0001] The invention belongs to the field of chemical medicines, in particular to a 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3- A method for preparing a methylammonium salt crystal form. Background technique [0002] Gastric acid-related disease is the most common type of disease in the digestive system. It refers to a general term for a type of digestive tract disease caused by excessive gastric acid secretion or being particularly sensitive to gastric acid. The common one is gastroesophageal reflux disease. , peptic ulcer, Zollinger-Ellison syndrome and digestive system diseases caused by non-steroidal anti-inflammatory drugs. PPIs are currently the class of drugs with the strongest acid-suppressing effect, such as omeprazole, lansoprazole, pantoprazole, rabeprazole, etc. Due to the phenomenon of acid rebound at night in PPI, it affects the therapeutic effect. The emergence of potassium ion-competitive acid blockers (P-CAB) drugs has ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12C07C53/10C07C51/41A61K9/19A61P1/00A61P1/04
CPCA61K9/0019A61K9/19C07B2200/13C07D401/12
Inventor 秦引林王伟
Owner JIANGSU CAREFREE PHARM CO LTD
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