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Method for preparing silodosin

A technology of silodosin and dihydrogen, which is applied in the field of medicinal chemistry synthesis, can solve the problems of difficult purification and low yield, and achieve the effects of simplifying product purification procedures, improving product quality and improving production efficiency

Inactive Publication Date: 2017-08-01
北京天泰恒华医药技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In actual production, the above process reaction generates a large amount of impurity benzoic acid-(R)-3-{5-[2-(bis-{2-[2-(2,2,2-trifluoro-ethoxy) -phenoxy]-ethyl}-amino)-propyl]-7-cyano-2,3-dihydro-indol-1-yl}-propyl ester, resulting in low yield and not easy purification

Method used

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  • Method for preparing silodosin
  • Method for preparing silodosin
  • Method for preparing silodosin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: Preparation of silodosin

[0044] Step 1: Preparation of 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile

[0045] 1. Add 80L of water into a 200L reactor, add 6.2Kg of sodium carbonate and stir until clear;

[0046] 2. Add 50L of ethyl acetate, stir, add 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H- Indole-7-carbonitrile tartrate 10Kg, stirred for 2 hours;

[0047] 3. Stand still to separate the liquid, extract the aqueous phase with 20L ethyl acetate once, and combine the organic phase;

[0048] 4. The organic phase was washed twice with 15L saturated brine, and the organic phase was dried with anhydrous sodium sulfate for 4 hours;

[0049] 5. Suction filtration, the desiccant was washed with ethyl acetate; the solvent was collected under reduced pressure to obtain 7Kg of oil, which was 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3 -(Benzoyloxy)propyl]-1H-indole-7-carbonitrile, the yield is about 99%. ...

Embodiment 2

[0078] Embodiment 2: preparation of silodosin

[0079] Step 1: Preparation of 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile

[0080] 1. Add 80L of water into a 200L reactor, add 6.2Kg of sodium carbonate and stir until clear;

[0081] 2. Add 50L of ethyl acetate, stir, add 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H- Indole-7-carbonitrile tartrate 10Kg, stirred for 2 hours;

[0082] 3. Stand still to separate the liquid, extract the aqueous phase with 20L ethyl acetate once, and combine the organic phase;

[0083] 4. The organic phase was washed twice with 15L saturated brine, and the organic phase was dried with anhydrous sodium sulfate for 4 hours;

[0084] 5. Suction filtration, the desiccant was washed with ethyl acetate; the solvent was collected under reduced pressure to obtain 7Kg of oil, which was 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3 -(Benzoyloxy)propyl]-1H-indole-7-carbonitrile, the yield is about 99%. ...

Embodiment 3

[0113] Embodiment 3: preparation of silodosin

[0114] Step 1: Preparation of 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile

[0115] 1. Add 80L of water into a 200L reactor, add 6.2Kg of sodium carbonate and stir until clear;

[0116] 2. Add 50L of ethyl acetate, stir, add 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H- Indole-7-carbonitrile tartrate 10Kg, stirred for 2 hours;

[0117] 3. Stand still to separate the liquid, extract the aqueous phase with 20L ethyl acetate once, and combine the organic phase;

[0118] 4. The organic phase was washed twice with 15L saturated brine, and the organic phase was dried with anhydrous sodium sulfate for 4 hours;

[0119] 5. Suction filtration, the desiccant was washed with ethyl acetate; the solvent was collected under reduced pressure to obtain 7Kg of oil, which was 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3 -(Benzoyloxy)propyl]-1H-indole-7-carbonitrile, the yield is about 99%. ...

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Abstract

The invention relates to a method for preparing silodosin, especially to an industrial preparation method of a silodosin compound, and belongs to the field of pharmaceutical chemical synthesis. The method includes: carrying out salt hydrolysis on 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile tartrate to obtain 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile, preparing benzoic acid-R-3-[7-cyano-5-(2-{2-[2-(2,2,2-trifluoro-ethoxy)-phenoxyl]-ethylamino}-propyl)-2,3-dihydro-indole-1-yl]-propylester which is an intermediate, and finally performing a hydrolysis reaction to produce silodosin. According to the provided industrial production method of silodosin, the yield is high, purification becomes easy and the impurity content is low.

Description

technical field [0001] The invention relates to a method for preparing silodosin, in particular to an industrial preparation method of compound silodosin (silodosin), which belongs to the field of pharmaceutical chemical synthesis. Background technique [0002] 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. Japan's Jusheng Pharmaceutical Co., Ltd. and Daiichi Sankyo Pharmaceutical Co., Ltd. jointly applied for it, and it was first approved for marketing in Japan in May 2006. The trade name used is Urief. Subsequently, Jusheng and Daiichi Sankyo also authorized silodosin to Watson Pharmaceutical Company of the United States, which was approved by the US Food and Drug Administration (FDA) in August 2008 and launched in the United States. The silodosin capsule preparation imported by Japan's Daiichi Sankyo Pharmaceutical Co., Ltd. wa...

Claims

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Application Information

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IPC IPC(8): C07D209/08
CPCC07D209/08
Inventor 李学钦刘文辉
Owner 北京天泰恒华医药技术有限公司
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