Synthesis method of silodosin dialkyl compound

A technology of silodosinic dialkyl and compound, which is applied in the field of pharmacy, can solve the problems of difficult reaction of amides, many impurities, difficult purification and the like, and achieves the effects of simple preparation method, high purity and improved quality standards

Active Publication Date: 2015-04-29
CHINA RESOURCES SAIKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the process of our synthesis of dialkylation, we found that the hydrolysis of the last step of amide is difficult to react, and when it is changed to severe conditions, there will be more impurities and it is difficult to purify

Method used

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  • Synthesis method of silodosin dialkyl compound
  • Synthesis method of silodosin dialkyl compound
  • Synthesis method of silodosin dialkyl compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1. Synthesis of 1-(3-hydroxypropyl)-5-[(2R)-2-(N,N-bis{2-[2-(2,2,2-trifluoroethoxy)benzene Oxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide

[0037] In turn, 1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino] Propyl]-2,3-dihydro-1H-indole-7-carboxamide (2.0g), 1-(2-bromoethoxy)-2-(2,2,2-trifluoroethoxy ) Benzene (3.0g), dimethylformamide (15mL) and potassium carbonate (1.7g) were added to a 100mL one-necked bottle. The mixture was warmed to 90 °C and stirred at reflux for 16 h. TLC monitoring (methanol / dichloromethane=1 / 10), cooled to room temperature, added EA (30 mL) and water (50 mL), stirred at room temperature for 10 min. The layers were separated, and the organic phase was washed with water (15 mL) and saturated NaCl (15 mL). After the solvent was evaporated to dryness, column chromatography purification (methanol / dichloromethane=1 / 10) gave 1-(3-hydroxypropyl)-5-[(2R)-2-(N,N-di{2-[2 -(2,2,2-Trifluoroethoxy)phen...

Embodiment 2

[0039] Example 2. Synthesis of 1-(3-hydroxypropyl)-5-[(2R)-2-(N,N-bis{2-[2-(2,2,2-trifluoroethoxy)benzene Oxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide

[0040]In turn, 1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino] Propyl]-2,3-dihydro-1H-indole-7-carboxamide (2.0g), 1-(2-bromoethoxy)-2-(2,2,2-trifluoroethoxy ) Benzene (3.0g), dimethylformamide (15mL) and sodium carbonate (1.3g) were added to a 100mL single-necked bottle. The mixture was warmed to 90 °C and stirred at reflux for 16 h. TLC monitoring (A / II=1 / 10), cooled to room temperature, added EA (30 mL) and water (50 mL), stirred at room temperature for 10 min. The layers were separated, and the organic phase was washed with water (15 mL) and saturated NaCl (15 mL). After the solvent was evaporated to dryness, column chromatography purification (methanol / dichloromethane=1 / 20) gave 1-(3-hydroxypropyl)-5-[(2R)-2-(N,N-di{2-[2 -(2,2,2-Trifluoroethoxy)phenoxy]ethyl}amino)propy...

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Abstract

The invention belongs to the field of pharmacy, and relates to a silodosin dialkyl compound, which is a silodosin impurity, and a synthesis method thereof. The silodosin dialkyl compound is specifically 1-(3-hydroxypropyl)-5-[(2R)-2-(N, N-di{2-[2-(2, 2, 2-trifluoroethoxyl) phenoxy]ethyl}amino) propyl]-2, 3-dihydro-1H-indolyl-7-formamide.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a silodosin impurity silodosin dialkyl compound and a synthesis method thereof. Background technique [0002] Silodosin, chemical name: 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethyl) Oxygen)phenoxy]ethylamino]propyl]-1H-indole-7-carboxamide, molecular formula: C25H32F3N3O4. [0003] Silodosin is an α1-receptor antagonist invented by Japan's Kissei Pharmaceutical Company, which can be used to treat symptoms associated with benign prostatic hyperplasia (BPH) or hypertrophy. Kissei and the first pharmaceutical (Daiich iSankyo) Co., Ltd. applied for it, and it was approved for marketing in Japan in May 2006. Kissei has also licensed silodosin to Watson Pharmaceuticals of the United States, which was most recently approved by the FDA in August 2008. [0004] Benign prostatic hyperplasia (BPH) is one of the common diseases in elderly men, characterized by non-malignant ...

Claims

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Application Information

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IPC IPC(8): C07D209/08
CPCC07D209/08
Inventor姚鹏宋波刘沫毅白沙沙
OwnerCHINA RESOURCES SAIKE PHARMA