1365546-05-9Relevant academic research and scientific papers
Preparation method of dronedarone hydrochloride key intermediate
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Paragraph 0022-0025, (2016/10/08)
The invention relates to a preparation method of a dronedarone hydrochloride key intermediate. The preparation method comprises following steps: 1) 2-butyl-benzofuran-5-ylamine hydrochloride and phthalic anhydride are subjected to reflux reaction under alkaline conditions so as to protect amino groups; and 2) 4-[3-(dibutyl amino) propoxy] benzoic acid is added into Eaton's reagent for stirring reaction, an intermediate 1 is added, temperature is controlled for reaction, a free amine is obtained via treatment, and the free amine and oxalic acid are subjected to salt forming reaction so as to obtain compound IV 5-amino-2-n-butyl-3-[4-(3-n-dibutyl aminopropoxy) benzoyl]benzofuran oxalate. The dronedarone hydrochloride key intermediate is prepared by taking 2-butyl-benzofuran-5-ylamine hydrochloride as the starting raw material; production of the dronedarone free amino is high in selectivity, and high in yield; fewer steps are needed; so that the preparation method is suitable for industrialized production.
An improved scalable route to pure dronedarone hydrochloride
Hivarekar, Raghvendra R.,Deshmukh, Sanjay S.,Tripathy., Narendra K.
experimental part, p. 677 - 681 (2012/08/07)
An efficient scalable synthesis for dronedarone hydrochloride (2) via Friedel-Craft acylation of 2-(-2-butyl-1-benzofuran-5-yl)-1H-isoindole-1,3(2H) dione (12) with 4-(3-chloropropoxy) benzoic acid (13) in good yield and high purity has been developed by using Eaton's reagent instead of hazardous and toxic metal halide catalyst like AlCl3 or SnCl4.
