40877-19-8Relevant articles and documents
A Facile Total Synthesis of Mubritinib
Wang, Rong,Cui, Menghan,Yang, Qing,Kuang, Chunxiang
supporting information, p. 978 - 982 (2021/02/03)
A five-step, practical, and concise total synthesis of mubritinib is described. The synthesis utilized Friedel-Crafts acylation, click reaction, reduction, and demethylation for the construction of the triazole ring system as key steps. Another important feature of this synthesis is the Bredereck oxazole synthesis. The main advantages of this process are the improved yield and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of mubritinib.
Synthesis method of mubritinib triazole intermediate
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Paragraph 0028-0033; 0048-0119, (2020/12/06)
The invention discloses a method for synthesizing a mubritinib triazole intermediate by taking propiolic acid as a raw material through a Click reaction. The method comprises the following steps: 1, taking anisole as a raw material, and carrying out a Friedel-Crafts acylation reaction with 4-chlorobutyryl chloride to obtain gamma-chloro-4-methoxyphenylbutanone, 2, enabling the gamma-chloro-4-methoxyphenylbutanone to react with sodium azide, propiolic acid, a copper catalyst, sodium ascorbate, an alkali and a solvent, so as to obtain 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone,3, reducing carbonyl into methylene by 1-(4-methoxyphenyl)-4-(1H-1, 2, 3-triazole-1-yl)-1-butanone in a trifluoroacetic acid/triethylsilane system, and 4, carrying out demethylation on the 1-[4-(4-methoxyphenyl)butyl]-1H-1, 2, 3-triazole by using 40% hydrobromic acid to obtain the mubritinib intermediate 4-[4-(1H-1, 2, 3-triazole-1-yl)butyl]phenol. The method greatly shortens the reaction path, and has the advantages of accessible raw materials, mild reaction conditions, high yield and the like, and is simple to operate.
Synthesis of nitrogenated heterocycles by asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines
Pablo, Oscar,Guijarro, David,Yus, Miguel
, p. 9181 - 9189 (2013/10/08)
Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl) haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.
