Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Crystal form A of brexpiprazole laurate, preparation method and application thereof

A technology of ebiprazole and laurate, applied in the field of medicinal chemistry, can solve the problems of low yield and long reaction time

Active Publication Date: 2019-09-10
SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT +1
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Otsuka Pharmaceutical Co., Ltd. reported the synthesis method of ebiprazole derivatives through patents, and the patents related to ebiprazole laurate mainly include US9260420B2, US9539252B2, US2015045356A1, US2016143905A1, US2017071933A1, CN201280043980.2, etc. Consistently shows that the obtained ebiprazole laurate is a brown oil, and the reaction time is long and the yield is low

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Crystal form A of brexpiprazole laurate, preparation method and application thereof
  • Crystal form A of brexpiprazole laurate, preparation method and application thereof
  • Crystal form A of brexpiprazole laurate, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Embodiment 1: the preparation of ebiprazole laurate

[0075]

[0076] Take 1.00 g of ebiprazole in a 50 mL three-necked flask, dissolve it with 20 mL of 1,4-dioxane until clear, and then add 0.28 g of NaH. After stirring at room temperature for 15 minutes, 1.14 g of chloromethyl laurate was added dropwise with an addition funnel, and 0.10 g of KI was added. The reaction solution was heated to 90° C., stirred for 2 h, then cooled to room temperature, and then quenched by pouring the reaction solution into a mixed solution of ethyl acetate and ice water. Finally, the mixed solution was transferred to a separatory funnel for separation, and the upper layer was washed twice with saturated sodium chloride solution, and then the remaining water was removed with anhydrous sodium sulfate, and about 1.50 g of crude ebiprazole laurate was obtained after spin-drying. 1 HNMR (400MHz, CDCl 3 ): δ7.61(d, J=9.5Hz, 1H), 7.54(d, J=8.0Hz, 1H), 7.40(dt, J=13.5, 7.1Hz, 3H), 7.26(t, J=...

Embodiment 2

[0077] Example 2: Preparation of Form A of Ebiprazole Laurate

[0078]Take 1 g of ebiprazole laurate prepared in Example 1, and add 10 mL of ethyl acetate to form a solution. Slowly add 10 mL of n-hexane dropwise at a low temperature of -20°C and a stirring speed of 100 rpm, and keep stirring at low temperature for 2 h to gradually precipitate a white solid. The white solid was obtained by suction filtration, washed twice with 5 mL of n-hexane, and dried in a vacuum oven at -0.08 Mpa, 40°C for 2 hours to obtain the crystal form A of ebiprazole laurate with a yield of 84.7%. Its content was determined to be 99.62% by high performance liquid chromatography. Specific conditions for HPLC: Welch for chromatographic column LP-C18 (250*4.6mm, 5μm), column temperature 40°C; mobile phase A is pure acetonitrile, mobile phase B is 0.15% triethylamine aqueous solution (pH 3.50), mobile phase A:B is 90:10 ; The injection volume is 10μL; the flow rate is 1.2mL / min; the detection wavelen...

Embodiment 3

[0079] Example 3: Preparation of Form A of Ebiprazole Laurate

[0080] Take 1 g of ebiprazole laurate prepared in Example 1, and add 10 mL of ethyl acetate to form a solution. Slowly add 20 mL of n-hexane dropwise at a low temperature of -20°C and a stirring speed of 100 rpm, and keep stirring at low temperature for 2 hours to gradually precipitate a white solid. The white solid was obtained by suction filtration, washed twice with 5 mL of n-hexane, placed in a vacuum oven at -0.08 Mpa, and dried at 40°C for 2 hours to obtain crystalline form A of ebiprazole laurate with a yield of 85.7%. Its content was determined to be 99.83% by high performance liquid chromatography.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a crystal form A of brexpiprazole laurate as shown as a formula I, a preparation method and application thereof. Characteristic peaks of an X-ray powder diffraction diagram ofthe crystal form A of brexpiprazole laurate, represented by 2theta, are 3.7+ / -0.2, 6.4+ / -0.2, 11.2+ / -0.2, 12.7+ / -0.2, 14.8+ / -0.2, 15.0+ / -0.2, 18.5+ / -0.2, 19.0+ / -0.2, 19.7+ / -0.2, 20.2+ / -0.2, 21.7+ / -0.2and 23.4+ / -0.2 degrees. The crystal form A prepared by the method has high purity, a proper melting point and good stability, can be dissociated easily to obtain brexpiprazole, has extremely low water solubility, has higher lipid solubility and better slow release effects than brexpiprazole, is suitable for development of long-acting preparations and has a good market application prospect.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a crystal form A of ebiprazole laurate, a preparation method and application thereof. Background technique [0002] On July 31, 2009, the FDA approved Invega, a long-acting injection of the second-generation anti-schizophrenia drug paliperidone developed by Janssen. It is used for the treatment of the acute phase and maintenance phase of schizophrenia, and it was launched in my country in 2012. Its main component, paliperidone palmitate (Paliperidone Palmitate), is an ester compound synthesized from paliperidone and palmitic acid using prodrug technology. On October 5, 2015, the FDA approved the long-acting injection of Aipiprazole Luroxil from Alkemes Its main component is also lauroyloxymethyl aripiprazole prepared by prodrug technology. [0003] The Chinese chemical name of Brexpiprazole is 7-(4-(4-(benzo[b]thiophene)-4-yl-piperazin-1-yl)butoxy)-1H-quinoline...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D409/12A61K31/496A61P25/18A61P25/24
CPCC07D409/12C07B2200/13
Inventor 何军王君吉王哲烽李昌盛成佳佳曾馨杨亚妮刘洁王笑笑周思维益兵王圣利牛明浩
Owner SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com