1228879-37-5Relevant articles and documents
Preparation method of tofacitinib intermediate cis-1-benzyl-N, 4-dimethylpiperidine-3-amine dihydrochloride
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, (2021/01/29)
The invention discloses a preparation method of a tofacitinib intermediate cis-1benzyl-N, 4-dimethyl piperidine-3-amine dihydrochloride. The synthetic method comprises the following steps: taking 3-bromo-4-methylpyridine as an initial raw material, performing substitution reaction with amine to obtain a compound III, and performing acetyl or tert-butyloxycarbonyl protection and catalytic hydrogenation on the compound III to obtain a piperidine compound V. The compound V and benzaldehyde are subjected to reductive amination or react with benzyl halide to obtain a compound VI. A protecting groupis removed from the compound VI, and a hydrochloride compound I. 2HCl is formed at the same time. The synthesis method is simple to operate, high in total yield, high in product purity, stable in quality and suitable for industrial production.
Preparation methods of tofacitinib citrate intermediate and tofacitinib citrate
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, (2020/01/25)
The invention discloses preparation methods of a tofacitinib citrate intermediate and tofacitinib citrate. The preparation method of the tofacitinib citrate intermediate comprises: preparing N-(1-benzyl-4-methyl-1,2,5,6-tetrahydropiperidine-3-yl)acetamide by using 3-amino-4-methyl-pyridine, acetyl chloride, benzyl chloride and sodium borohydride as raw materials; preparing 1-benzyl-N,4-dimethylpiperidine-3-amine by using the N-(1-benzyl-4-methyl-1,2,5,6-tetrahydropiperidine-3-yl)acetamide, hydrochloric acid, methylamine and sodium borohydride as raw materials; and carrying out resolution and dissociation on the 1-benzyl-N,4-dimethylpiperidine-3-amine, and carrying out salt forming with hydrochloric acid to obtain the product. The invention provides the new tofacitinib citrate intermediatepreparation method, wherein the use amount of the catalytic hydrogenation catalyst is reduced in the preparation process of tofacitinib citrate so as to reduce the cost, and the generation of N-alkylated impurities can be well controlled by adopting the isopropanol/water mixed solvent.
PROCESS FOR THE PREPARATION OF CHIRAL 3-AMINO-PIPERIDINS, USEFUL INTERMEDIATES FOR THE PREPARATION OF TOFACITINIB
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, (2019/01/15)
Object of the present invention is an improved process for the preparation of (3R,4R)-1-benzyl-4-methylpiperidin-3-amine by means of chiral Rhodium catalysts.