Preparation and analysis methods of benzimidazole derivative
A technology of benzimidazole and its derivatives, which is applied in the field of preparation of pharmaceutical compounds, and can solve problems such as environmental pollution and potential safety hazards
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Example Embodiment
[0115] Preparation Example 1
[0116] According to the method before column chromatography described in Example 13 of Patent Application 201410010180.1, 10 kg of the pure compound of the following formula 4-1 was dissolved in 200 L of DMF, 21.2 kg of Azilsartan and 25 kg of cesium carbonate were added under stirring, and then the temperature was raised to 40°C, maintaining this temperature for 24 hours. TLC monitoring the reaction showed that the compound of formula 4-1 had almost completed the reaction, the temperature of the reaction solution was lowered to room temperature, 1000L of water was added, extracted with ethyl acetate (200L*3), the organic phases were combined and washed with saturated aqueous sodium chloride solution (100L*2 ), dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, to obtain 20kg mixture, which is an oily substance containing the compound of formula 5 and rearrangement impurity compound 5-1 thereof, wherein the content...
Example Embodiment
[0118] Example 1
[0119] 1) Add 40 L of butanol to about 10 kg of the crude oil product of the compound of formula 5, heat up to 80° C. to dissolve, and cool to room temperature for crystallization overnight. Filter, collect the solid, rinse the filter cake with 2.0 L of butanol, and dry under reduced pressure to obtain 9.5 kg of the product, the yield is 95.0% (calculated as the crude oil of the compound of formula 5), and the product purity is 87.0%;
[0120] 2) Add 18.4L of tert-butanone to 9.5kg of the compound solid of formula 5 after the previous step of recrystallization, beating at room temperature for 2h, filter, and dry under reduced pressure to obtain 8.64kg of product with a purity of 99.2% and a yield of 90.9%, wherein the rearranged impurity content is 0.42%, less than 0.50%.
Example Embodiment
[0121] Example 2
[0122] 1) To about 13 kg of the crude oil product of the compound of formula 5, add 52 L of ethanol with a mass percentage of 75%, and heat up to 60° C. to dissolve for 2 hours. Slowly cool to room temperature and crystallize overnight. Filter, collect the solid, rinse the filter cake with 2L 75% ethanol, and dry under reduced pressure to obtain 11.1 kg of product with a yield of 85.4% (calculated as crude oil of the compound of formula 5) and a product purity of 87.6%.
[0123] 2) Add 110L of methyl isobutyl ketone to the solid 11.1Kg of the compound of formula 5 after the previous step of recrystallization, heat to 80° C. to dissolve all, cool to room temperature for crystallization overnight, filter, and dry under reduced pressure to obtain 9.6kg of the compound product of formula 5 , the purity is 99.4%, the yield is 86.5%, and the rearranged impurity content is 0.38%, less than 0.50%.
PUM
Abstract
Description
Claims
Application Information
- R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap