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Method for preparing ropinirole hydrochloride

A technology of ropinirole hydrochloride and ethanol, which is applied in the field of preparation of ropinirole hydrochloride, can solve the problems of complex reaction and low yield, and achieve the effects of simple preparation process, high yield and low cost

Inactive Publication Date: 2018-08-24
CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this route is very mature, the reactions involved are relatively complicated and the yield is too low

Method used

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  • Method for preparing ropinirole hydrochloride
  • Method for preparing ropinirole hydrochloride
  • Method for preparing ropinirole hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Embodiment 1: synthetic compound 4

[0074]1. Compound 3 was divided into 15 groups, each group 39 mg. Using a dry round-bottomed flask as a reaction vessel, dissolve compound 3 in each group of solvents (subject to complete dissolution) at a temperature of -40°C to 80°C, slowly add 1.1 equivalents of component 1, and then slowly add 1.1 Equivalent of component 2, continue to stir the reaction for no more than 30 seconds. TLC monitors that the reaction is complete, adding water with a volume 5 to 10 times the volume of the solvent, extracting 3 times with ethyl acetate, combining the organic phases and then extracting with saturated brine, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain a crude product, and passing through the column Chromatographic purification afforded compound 4.

[0075] The specific parameters and effects of each group are shown in Table 1.

[0076] Each concrete parameter and yield of synthetic compound 4 of...

Embodiment 2

[0080] Embodiment 2: synthetic compound 5

[0081] 1. Divide compound 4 into 6 groups, each 42 mg, using a dry two-necked bottle as a reaction vessel, under hydrogen ambient conditions, dissolve each group of compound 4 in a solvent (subject to complete dissolution), add at room temperature Pd / C of different quality, continue stirring reaction for about 2 hours. The completion of the reaction was monitored by TLC, and the solid was filtered off with diatomaceous earth. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by column chromatography to obtain compound 5.

[0082] The specific selection of solvent, the amount of Pd / C and the effect are shown in Table 2, wherein the amount of Pd / C refers to the ratio (%) of the mass of Pd / C to the mass of compound 4.

[0083] Table 2 The specific parameters and yields of synthetic compound 5

[0084] group

Solvent (2mL)

Pd / C dosage

Yield of Compound 5

group ...

Embodiment 3

[0087] Embodiment 3: synthetic compound 6

[0088] 1. Divide compound 5 into 4 groups, 35 mg in each group, use a dry round bottom flask as a reaction vessel, dissolve each group of compound 5 in dichloromethane (group 1), chloroform (group 2), 1,2-dichloroethane (group 3), pyridine (group 4) (subject to complete dissolution), add 1.2 equivalents of pyridine at room temperature, then add 1.2 equivalents of p-toluenesulfonyl chloride, continue to stir and react for about 2 hours. TLC monitored the reaction to be complete, adding 1N hydrochloric acid solution to quench the reaction, using ethyl acetate to extract 3 times, combining the organic phases and then extracting with saturated brine, drying with anhydrous sodium sulfate, concentrating under reduced pressure to obtain a crude product, and then purifying by column chromatography Compound 6 was obtained.

[0089] 2. The effects of each group are shown in Table 3.

[0090] Table 3 shows the effect of synthesizing compound...

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Abstract

The invention belongs to the technical field of medicinal chemistry and organic chemistry, and particularly relates to a method for preparing ropinirole hydrochloride. A novel compound 4 is synthesized by the aid of the method and is used as a raw material for preparing the ropinirole hydrochloride. The particular method includes dissolving the compound 4 in one or a plurality of types of ethyl alcohol / methanol / ethyl acetate to obtain liquid, adding Pd / C into the ethyl alcohol / methanol / ethyl acetate, and carrying out reaction to obtain compounds 5; dissolving the compounds 5, p-toluenesulfonylchloride and pyridine in one or a plurality of types of dichloromethane / trichloromethane / 1, 2-dichloroethane / pyridine, and carrying out reaction to obtain compounds 6; dissolving the compounds 6, NaIand dipropyl amine in one or a plurality of types of DMF (dimethyl formamide) / DMSO (dimethylsulfoxide) / Toluene, and carrying out reaction to obtain ropinirole; dissolving the ropinirole in 1, 4 dioxane with hydrochloric acid, and carrying out reduced-pressure compression to obtain the ropinirole hydrochloride. A proportion of the compounds 5 to the p-toluenesulfonyl chloride to the pyridine is equal to 1:1.2:1.2. A proportion of the compounds 6 to the NaI to the dipropyl amine is equal to 1:1:1.2. The novel method for preparing the ropinirole hydrochloride has the advantages that the method includes simple and convenient steps and can be practically put into production, and raw materials for the ropinirole hydrochloride are simple and are easily available.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and organic chemistry, and in particular relates to a preparation method of ropinirole hydrochloride. Background technique [0002] The drug Ropinirole Hydrochloride, also known as 4-[2-di-n-propylaminoethyl]-1,3-dihydro-2H-indol-2-one hydrochloride, was developed by Smithkline Beecham , which was first listed in the UK in 1996, was first approved for the treatment of Parkinson's disease in 1997, and belongs to the second generation of powerful dopamine receptor agonist drugs (Dopamine Agonist). Its pharmacological research shows that the drug can enhance the effect of dopamine, correct the imbalance of central neurotransmitters, relieve symptoms and maintain the patient's autonomy and activity, the effect is remarkable, and it has neuroprotective function. Moreover, it reduces the occurrence of dyskinesias compared with levodopa. In addition, ropinirole hydrochloride can also be use...

Claims

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Application Information

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IPC IPC(8): C07D209/34
CPCC07D209/34
Inventor 邵华武梁鹏
Owner CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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