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Indoline compound for preparing silodosin and preparation method thereof

A compound, indoline technology, applied in the direction of organic chemistry, can solve the problems of low chiral induction rate and small steric hindrance of protecting groups, and achieve the effects of high induction rate, easy industrial production, and high overall yield

Active Publication Date: 2011-03-30
ZHEJIANG HUAHAI PHARMACEUTICAL CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compound (IX) reacts asymmetrically with L-(S)-phenylglycinol under the catalysis of platinum oxide, which may be due to the small steric hindrance of the protecting group and the low chiral induction ratio of 3.8:1

Method used

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  • Indoline compound for preparing silodosin and preparation method thereof
  • Indoline compound for preparing silodosin and preparation method thereof
  • Indoline compound for preparing silodosin and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: the preparation of compound (III)

[0039] 264 grams of 4-fluorobenzoic acid was dissolved in 550ml of DMF. Put 375ml of bromochloropropane, 265ml of triethylamine, and 300ml of DMF in a reaction flask, add 4-fluorobenzoic acid dropwise at room temperature, and react at room temperature for 12h. Add water, extract with ethyl acetate, wash the organic layer with saturated aqueous sodium bicarbonate solution and brine, dry the organic layer with anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain oil compound (II)

[0040] The mass spectrometry of the oil showed that the molecular ion peak [M+1] was 217.

[0041] Compound (II) 391 grams, diisopropylethylamine 473ml, indoline 182ml) and DMF1600ml, stirred at 105°C for 16 hours. Added water, extracted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, and brine, organic The layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduce...

Embodiment 2

[0044] Example 2: 1-(3-(4-methylbenzoyloxy)propyl)indoline hydrochloride

[0045] With reference to the preparation method of Example 1, replace 4-fluorobenzoic acid with 4-methylbenzoic acid, and other reagents and operations remain unchanged, and react to obtain 1-(3-(4-methylbenzoyloxy) Propyl)indoline hydrochloride.

[0046] 1NMR spectrum (DMSO-d6): δppm 2.0-2.1 (2H, m), 2.3-2.4 (3H, s), 2.9-3.1 (2H, t), 3.33-3.35 (2H, t), 3.45-3.5 (2H , t), 4.3-4.4 (2H, t), 6.5-6.6 (2H, d), 6.9-7.1 (2H, m), 7.2-7.5 (2H, m), 7.8-8.0 (2H, m)

Embodiment 3

[0047] Embodiment 3: the preparation of compound (IV)

[0048] N 2Protected, ice-salt bath, 11ml of phosphorus oxychloride was added dropwise to 37ml of DMF, then 20g of compound (III) was added, and reacted at room temperature for 3 hours. The reaction solution was poured into water to precipitate a solid and dried to obtain compound (IV). (yield 95%)

[0049] Melting point: 66~68℃

[0050] 1 NMR spectrum: 1 NMR spectrum (DMSO-d6): δppm 2.0-2.1 (2H, m), 2.9-3.1 (2H, t), 3.3-3.4 (2H, t), 3.5-3.6 (2H, t), 4.3-4.4 (2H , t), 6.4-6.6 (1H, dd), 7.3-7.5 (4H, m), 8.0-8.1 (2H, m), 9.5-9.6 (1H, s)

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Abstract

The invention provides an indoline compound of 1-(3-substituted benzoyl alkoxypropyl)-5-(2-nitrylpropyl)-7-cyanophoric indoline and a preparation method thereof. The indoline compound can be used as an intermediate compound and is used for synthesizing silodosin. The indoline compound uses substituted phenylformic acid as a raw material, is prepared by multiple-step reaction, has high yield and is easy to industrially produce.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a novel compound for synthesizing silodosin, a drug for treating hyperplasia of the prostate gland, and a preparation method thereof. Background technique [0002] 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. At present, there are many reports on the synthesis methods of silodosin, but there is a lack of methods with high yield and suitable for industrial production. [0003] JP200199956 has reported that benzoic acid is used as raw material to prepare 1-(3-benzoyloxypropyl)indoline hydrochloride (such as structural formula (1), R is a hydrogen atom), with a yield of 60%. Multi-step reaction further produces silodosin intermediate 1-(3-benzoyloxypropyl)-5-(2-nitropropyl)-7-cyanoindoline (s...

Claims

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Application Information

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IPC IPC(8): C07D209/08C07C69/78
Inventor 王小梅王哲烽隋强刘启皓时惠麟
Owner ZHEJIANG HUAHAI PHARMACEUTICAL CO LTD
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