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Silodosin intermediate, preparation method of silodosin intermediate and method for preparing silodosin from silodosin intermediate

A technology for silodosin and intermediates, which is applied in the field of compound synthesis and can solve the problems of multiple impurities, harsh purification conditions, low yield, high price of lithium tetrahydroaluminum and the like

Active Publication Date: 2015-07-01
ANHUI QINGYUN PHARMA & CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

with Na 2 CO 3 , NaBH 4 , EtOH reaction to obtain silodosin, the reaction route is long, the purification conditions are harsh, and lithium aluminum hydride is expensive, and it is easy to explode and decompose when exposed to water, so it is not suitable for large-scale industrial production
[0007] Xiao Chuan Luo et al. (Chin Chem Lett, 19(1):59-60, 2008) reported that 2-(2, 2,2-trifluoroethoxy)phenol, and then react with 1,2-dibromoethane to obtain 2-(2,2,2,-trifluoroethoxy)phenyl bromoethyl ether, and react to obtain Lodosin, this reaction route is long, and yield is low, and the four-step reaction yield is only 26%

Method used

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  • Silodosin intermediate, preparation method of silodosin intermediate and method for preparing silodosin from silodosin intermediate
  • Silodosin intermediate, preparation method of silodosin intermediate and method for preparing silodosin from silodosin intermediate
  • Silodosin intermediate, preparation method of silodosin intermediate and method for preparing silodosin from silodosin intermediate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] The preparation of the compound shown in embodiment 1 formula II

[0121] The preparation of compound shown in formula III:

[0122] raw material:

[0123] a. Benzyl chloride (M=126.5) 1265g (10.0mol)

[0124] b. Indoline (M=119.17) 596g (5.0mol)

[0125] c. Water 1Kg (55.5mol)

[0126] d. Sodium bicarbonate (M=84) 840g (10.0mol)

[0127] Feeding: a:b:d=2:1:2 (molar ratio), a, b reactants, c, d are catalysts.

[0128] Add a, c, and d into a 3L reaction flask, raise the temperature to 60-90°C, add b dropwise to the reaction solution, stir at 95°C for 1 hour after the drop, and detect by HPLC.

[0129] After the reaction, add 2L of toluene to the reaction solution, stir and separate layers, wash the organic layer once with 1L of water, dry, filter, and concentrate to obtain 1.17Kg (87.9%) of the compound represented by formula III.

[0130] The preparation of compound shown in formula IV:

[0131] raw material:

[0132] a. Dimethylformamide (M=73.09) 730.9Kg (10.0...

Embodiment 2

[0166] The preparation of embodiment 2 silodosin

[0167] The preparation of compound shown in formula VIII:

[0168] raw material:

[0169]

[0170] Feeding: a:e=1:45.6; a and e are reactants, b is catalyst, c and d are solvents.

[0171] Add a, c, d, and e into the reaction flask, stir for half an hour, then add b into it, after adding b, start to flow hydrogen, and after passing hydrogen for one minute, raise the temperature to 60°C for 1 hour, HPLC detection, raw materials After the reaction is complete, it can be processed.

[0172] After cooling the reaction liquid to room temperature, filter and remove the catalyst, add 150ml of ethyl acetate to the filtrate, adjust the pH to PH ≥ 8 with ammonia water, stir for half an hour, retest the pH, separate layers, and then use 100ml of acetic acid in the water layer Extracted once with ethyl ester, combined the organic layers, washed twice with 50ml of saturated brine, dried, filtered, and concentrated to obtain 1.96g of ...

Embodiment 3

[0188] Preparation of compound shown in embodiment 3 formula II

[0189] The preparation of compound shown in formula III:

[0190] raw material:

[0191] a. Benzyl chloride (M=126.5) 2530g (20.0mol)

[0192] b. Indoline (M=119.17) 596g (5.0mol)

[0193] c. Water 1Kg (55.5mol)

[0194] d. Sodium bicarbonate (M=84) 1680g (20.0mol)

[0195] Feeding: a:b:d=4:1:4 (molar ratio), a, b are reactants, c, d are catalysts.

[0196] Add a, c, and d into a 3L reaction bottle and raise the temperature to 60-90°C, add b dropwise to the reaction solution, stir at 95°C for 14 hours after the drop, and detect by HPLC.

[0197] After the reaction was completed, 2 L of toluene was added to the reaction liquid, the layers were stirred and separated, the organic layer was washed once with 1 L of water, dried, filtered and concentrated to obtain 1.17 Kg (purity 87.9%) of the compound represented by formula III.

[0198] The preparation of compound shown in formula IV:

[0199] raw material: ...

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Abstract

The invention relates to the field of compound synthesis and especially relates to a silodosin intermediate, a preparation method of the silodosin intermediate, and a method for preparing silodosin from the silodosin intermediate. The method for preparing silodosin from the silodosin intermediate has the characteristics of economy, safety, high purity and high yield and is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to the field of compound synthesis, in particular to a silodosin intermediate, a preparation method thereof, and a method for preparing silodosin by using the intermediate. Background technique [0002] The structure type of silodosin belongs to phenalkamine compounds. Its chemical name is: (R)-(-)-1-(3-hydroxypropyl)-5-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy ]ethylamino]propyl]-7-carbamoylindoline. The structural formula is as shown in formula I: [0003] [0004] Silodosin has a selective inhibitory effect on the contraction of urethral smooth muscle, and reduces the intraurethral pressure, but has no great effect on blood pressure, and is used for the treatment of benign prostatic hyperplasia. There are certain disadvantages in the currently existing technical routes for synthesizing silodosin, so there is a demand for innovative silodosin synthetic processes in this field. [0005] According to the synthetic route of si...

Claims

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Application Information

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IPC IPC(8): C07D209/08
CPCC07D209/08
Inventor 黄庆云黄欢黄庆国
Owner ANHUI QINGYUN PHARMA & CHEM
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