Prepn process of Ropinirole and derivative thereof

A compound and a representative technology, applied in the field of preparation of ropinirole and its derivatives, can solve the problems of eliminating a large number of by-products, high price, etc., and achieve the effects of saving production equipment and costs, short reaction steps, and high yield

Inactive Publication Date: 2009-04-22
浙江凯普化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this route is shorter than the first route, it is more suitable for preparing kilogram-scale ropinirole and its derivatives, but the price of the starting material V of this method is very expensive, and the last step reaction will produce a large amount of elimination by-products

Method used

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  • Prepn process of Ropinirole and derivative thereof
  • Prepn process of Ropinirole and derivative thereof
  • Prepn process of Ropinirole and derivative thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Preparation of β-methoxy-3-nitrostyrene (XI)

[0082] Methoxymethyltriphenylphosphine chloride (4.75g, 13.86mmol) and anhydrous tetrahydrofuran were mixed and cooled to 0°C, potassium tert-butoxide (1.94g, 17.33mmol) was added with stirring, and the resulting suspension continued to cool to -10°C, add dropwise a toluene solution of 3-nitrobenzaldehyde (1.74g, 11.55mmol) within 30 minutes, after dropping, keep stirring for 1h, add a saturated ammonium chloride solution dropwise at 0°C, and wash the mixture with ethyl acetate Ester extraction (20mL x 2), combined organic layers, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate. The solvent was evaporated to obtain a yellow solid, which was a mixture of cis and trans isomers, with a yield of 88%.

Embodiment 2

[0084] Preparation of 2-(3-nitrophenyl)acetaldehyde (XII)

[0085] Compound XI (17.90 g, 0.10 mol) was dissolved in THF, 2 mol / L HCl 60 ml was added with stirring, and the resulting mixture was heated at 80°C for reaction. THF was distilled off under reduced pressure, the residue was dissolved in ethyl acetate and water, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with 5% sodium bicarbonate and saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain the product with a yield of 95%.

Embodiment 3

[0087] Preparation of 3-(di-n-propylamino)ethylnitrobenzene (XIII)

[0088] Compound XII (23.39g, 0.14mol) was dissolved in a mixed solvent of THF and methanol, di-n-propylamine (24.70mL, 0.18mol) and sodium cyanoborohydride (12.47g, 0.20mol) were added accordingly, and the reaction mixture was heated at room temperature Stir the reaction. Add 50ml of 1mol / L HCl to terminate the reaction. The resulting mixture was evaporated under reduced pressure, the residue was extracted with ethyl acetate, the extract was washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate. After recovering the solvent, the residue was purified by column chromatography to obtain the target compound , yield 80%.

[0089] 1 H-NMR (CDCl 3 , 200MHz): δ 8.10(s1H), 8.05(d, 1H), 7.55(d, 1H), 7.49(t, 1H), 2.85(dd, 2H), 2.70(dd, 2H), 2.49(t, 4H ), 1.45(m, 4H), 0.90(t, 6H).

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Abstract

The invention relates to the fields of organic chemistry and medicinal chemistry, in particular to a preparation method of ropinirole (structural formula I) and derivatives thereof. The preparation method of the invention has simple reaction steps, low raw material cost and high product yield.

Description

technical field [0001] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular to a preparation method of ropinirole and derivatives thereof. Background technique [0002] Ropinirole chemical name: 4-[(2-dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one, structural formula: [0003] [0004] It is clinically used as a D2 receptor agonist for the treatment of hypertension. [0005] The preparation method of substituted indolinone derivatives, especially ropinirole (structural formula I) has been reported in previous literatures. Such as: US 4452808 discloses 4-aminoalkyl-2-(3H)-indolone compounds as D2 receptor agonists for the treatment of hypertension, these compounds have the following general structural formula II: [0006] [0007] Wherein R can be amino, short-chain hydrocarbon amino, di-short-chain hydrocarbon amino, allylamino, diallylamine, N-short-chain hydrocarbon-N-allylamine, benzylamino, dibenzylamino, benzene Ethyl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/34
Inventor 刘美正潘建林
Owner 浙江凯普化工有限公司
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