阅读说明：本技术 一种月桂酰阿立哌唑的制备方法 (Preparation method of lauroyl aripiprazole ) 是由 齐晓溪 李恩民 赵国磊 于 2018-08-01 设计创作，主要内容包括：本发明涉及一种化学药物——月桂酰阿立哌唑(式I)的合成方法。用7-[(4卤丁基)-2-氧-3,4-二氢喹啉酮-1(2<I>H</I>)-基]甲基十二烷酸酯经一步反应制得月桂酰阿立哌唑。该方法收率高,且纯度可以达到99.5%以上。<Image he="125" wi="260" file="100004_DEST_PATH_IMAGE001.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>I。(The invention relates to a synthetic method of a chemical drug, namely lauroyl aripiprazole (formula I). With 7- [ (4-halobutyl) -2-oxo-3, 4-dihydroquinolinone-1 (2) H ) -radical]The methyl dodecanoate is subjected to one-step reaction to prepare the lauroyl aripiprazole. The method has high yield and purity of over 99.5%. I。)

1. A method of synthesizing lauroyl aripiprazole having the following general formula (I):

a carbostyril compound represented by the formula (II):

wherein X represents a halogen atom, an arylsulfonyloxy group, with a piperazine compound represented by the formula (III) and/or a salt thereof in an organic reagent in the presence of an inorganic base,

2. the method according to claim 1, wherein the organic reagents used are: DMF and water.

3. The production method according to claim 1, wherein the method uses only one inorganic base, and the inorganic base compound is an alkali metal hydroxide, an alkali metal carbonate, or an alkali metal.

4. The process according to claim 1, wherein the inorganic base is used in an amount of 0.5 to 5 times by mole with respect to the compound II.

5. The process according to claim 1, wherein the reaction temperature is from 0 to 120 ℃, preferably from 80 to 105 ℃.

6. The method according to claim 1, wherein X in the structure of the compound II is a chlorine atom or a bromine atom.

7. The method according to claim 1, wherein X in the structure of compound II is p-toluenesulfonyloxy.

8. The process according to claim 1, wherein said compound III is 1- (2, 3-dichlorophenyl) piperazine and/or a salt thereof.

Technical Field

The invention belongs to the field of pharmaceutical chemistry, and relates to a preparation method of chemical medicine lauroyl aripiprazole.

Background

The chemical name of the cinnamyl aripiprazole is 7- {4- [4- (2, 3-dichlorophenyl-1-piperidyl) butoxy]-2-oxo-3, 4-dihydro-2 (1)H) -quinolinone-1-yl } methyldodecanoate, british name Aripiprazole Lauroxil, of the formula:

10 months 2015, the us FDA approved lauroyl aripiprazole (aripiprazole lauroxil, arista) sustained release injection from Alkerme company for the treatment of adult patients with schizophrenia.

Disclosure of Invention

Lauroyl aripiprazole is a novel aripiprazole LAIs approved by the FDA on the market 10 months 2015. At present, no patent report is made in all countries. The present invention will fill this gap.

A method of synthesizing lauroyl aripiprazole having the following general formula (I):

a carbostyril compound represented by the formula (II):

wherein X represents a halogen atom, an arylsulfonyloxy group, with a piperazine compound represented by the formula (III) and/or a salt thereof in an organic reagent in the presence of an inorganic base.

The organic reagent is DMF and water, the inorganic base compound is alkali metal hydroxide, alkali metal carbonate or alkali metal, the inorganic base is used in 0.5-5 times the molar amount of the compound II, the temperature is 0-120 deg.c, preferably 80-105 deg.c, the compound II has structure with X as chlorine atom and bromine atom and p-toluenesulfonyloxy radical, and the compound III is 1- (2, 3-dichlorophenyl) piperazine and/or its salt.

The reagents and starting materials used in the present invention are commercially available.

The invention has the positive improvement effect of providing a preparation method of lauroyl aripiprazole, and no report is available at present.

Detailed Description

The present invention is further illustrated by the following examples, but is not limited thereto.