- Preparation method of Bilastine intermediate
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The invention belongs to the technical field of medicine preparation and relates to a preparation method of a bilastine intermediate. The method sequentially comprises the following steps of: mixing and stirring a compound 7, dichloromethane and anhydrous aluminum trichloride; dropwise adding a compound 1, mixing and stirring a reaction product and trifluoroacetic acid; adding triethyl silane; mixing and stirring a product, obtained after temperature rise for reaction of the mixture, DMSO and water; mixing a product, obtained after temperature rise for reaction, with 2-amino-2-methylpropane-1-alcohol and toluene; and heating and stirring to perform a reaction, so as to obtain an off-white solid 4-[1-(4, 5-dihydro-4, 4-dimethyl-2-oxazolyl)-1-methyl ethyl] phenethyl alcohol; and finally making the off-white solid react with paratoluensulfonyl chloride to obtain a bilastine intermediate final product. The preparation method has the advantages of simple operation, mild reaction conditions, easy purification of the intermediate, reduction of three wastes, and industrial cost reduction.
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- A process for the preparation of the compared to the russ sandbank method (by machine translation)
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The invention relates to a process for the preparation method compared to the russ sandbank, including I [...] compound added to the water, to add a phase transfer catalyst, paratoluene sulfonyl chloride and sodium hydroxide, after stirring and reacting and filtration to obtain [...] sulfonic acid ester. The sulfonic acid ester added to the water, by adding 2 - (4 - piperidinyl) 1 - H - benzimidazole and phase-transfer catalyst, adding sodium carbonate or potassium carbonate, heating suspension reaction 3 - 5 hours, filtering the obtained intermediate II is added to the strong polar non-protic solvent, by adding sodium hydroxide, phase-transfer catalyst, ethylene glycol is added to the toluene sulfonic acid ester, - 20 - 60° stirring reaction after the end of the filter and wash the obtained intermediate III. The intermediate III into the organic acid aqueous solution, refluxing 3 - 5 hours, water addition, adding alkali saturated, solution reflux 3 - 5 hours, generated in the saturated [...] does not dissolve in the alkaline solution, extraction [...]. The method of mild reaction conditions, the operation is simple, environmental protection, high yield, is suitable for industrial production. (by machine translation)
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Paragraph 0022; 0024
(2019/05/11)
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- A new and competitive synthetic approach for an antihistamine agent, bilastine
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Efforts towards the novel synthesis of second generation non-sedating antihistamine drug, Bilastine was described in this manuscript. This competitive synthetic approach involves the convergent synthesis of Bilastine via simple Friedel-Crafts acylation as an alternate for earlier reported Stille and Suzuki couplings. The selectivity in Friedel-Crafts acylation reaction with chloro acetyl chloride on different substituted arenes was studied and employed the best conditions for the synthesis of Bilastine. Further synthetic approach involves the deoxygenation of aryl ketone to corresponding alkane in single step and finally provides Bilastine with 39% of improved overall yields, utilizing simple and cost-effective reagents, suitable for kilogram scale synthesis.
- Kommera, Rajashekar,Yerrabelly, Jayaprakash Rao,Kasireddy, Venkateshwarreddy,Ghojala, Venkat Reddy,Singavarapu, Adilakshmi,Rebelli, Pradeep
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p. 815 - 821
(2018/11/06)
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