477600-74-1Relevant articles and documents
Process for the preparation of tofacitinib and intermediates thereof
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, (2021/05/07)
Provided is a process for the preparation of high purity tofacitinib, which reduces formation of N-methyl impurity. The invention also provides novel intermediates used in the process to prepare tofacitinib. There is provided an improved process for the preparation of tofacitinib (I), comprising the steps of: adding cyanoacetic acid in molar equivalent 0.2-1.2 to compound of formula (II-S), followed by addition of carbodiimide coupling agent of formula (III), optionally reacting tofacitinib base with citric acid.
Synthesis method of tofacitinib citrate
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, (2021/12/07)
The invention discloses a tofacitinib citrate synthesis method, belongs to the technical field of tofacitinib citrate preparation, and can effectively inhibit activity of Janus and JAK1 JAK3, block signal transduction of various inflammatory cytokines, and has an expensive catalyst application in the existing synthesis step. The method uses 1 - benzyl -4 - methyl -3 - (methylamino) piperidine hydrochloride as a raw material to prepare the tofacitinib citrate as a raw material, and then the citric acid tofacitinib citrate is obtained through twice refining 4 -7 - and the - 7H - yield and 2 the 3 - D purity of the tofacitinib citrate are improved.
Short enantioselective total synthesis of (+)-tofacitinib
Mane, Kishor D.,Kamble, Rohit B.,Suryavanshi, Gurunath
supporting information, (2021/02/20)
An enantioselective total synthesis of Tofacitinib (CP-690,550), a Janus tyrosine kinase (JAK3) specific inhibitor has been achieved from the readily available 4-piperidone. Proline catalysed hydroxylation is the key step for the synthesis of enantiopure 1-benzyl-4-methylpiperidin-3-ol.
Preparation method of tofacitinib citrate
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, (2021/04/21)
The invention discloses a preparation method of tofacitinib citrate. The method comprises the following steps: by taking 7-tert-butyloxycarbonyl-4-amino-7H-pyrrolo[2, 3-D]pyrimidine and 1-benzyl-4-methyl-piperidine-3-ketone as initial raw materials, carrying out condensation under a weak acidic condition, then carrying out N methylation, selective reduction, debenzylation and Boc removal, and carrying out ester exchange and citric acid salification at a high temperature to obtain the tofacitinib citrate. The method has the advantages of mild reaction conditions, simple post-treatment mode, reduction of the generation amount of hazardous wastes, environmental protection, cost saving, and facilitation of industrial production.
Preparation method of tofacitinib hydrolysis impurity
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Paragraph 0043-0044, (2021/03/31)
The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a tofacitinib hydrolysis impurity. The method comprises the following steps: dissolving isopropyl malonate in an organic solvent, adding N-methyl-N-((3R,4R)-4-methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine, conducting stirring at room temperature until the reaction is finished, and recrystallizing the reaction solution to obtain the tofacitinib hydrolysis impurity. The synthesis method provided by the invention is simple, the tofacitinib hydrolysis impurity obtainedby the method is recrystallized for separation, the purity is high, the yield is high, and the impurity compound can be used as an impurity reference substance in tofacitinib finished product detection standards.
PROCESS FOR PREPARATION OF TOFACITINIB AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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, (2020/09/27)
The present invention relates to an improved process for preparation of tofacitinib (I) and pharmaceutically acceptable salt thereof. (I)
Preparation method of tofacitinib or salt thereof (by machine translation)
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, (2020/06/20)
The preparation method of the tofacitinib intermediate V compound comprises the following steps: (1) a compound II and a compound III are subjected to a photoreaction reaction to generate an intermediate IV; (2) an intermediate IV and a methylation reagent are subjected to methylation reaction to generate a compound of formula V; wherein R is. 1 And R2 Are each independently an amino protecting group. The preparation method disclosed by the invention does not need to be subjected to isomer resolution purification in the preparation method, avoids using tetrahydroaluminum hydride, is low in synthesis cost, high in yield, simple in reaction condition and post-treatment operation and suitable for industrial production. (by machine translation)
Improved tofacitinib synthesis method and impurity preparation method (by machine translation)
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Paragraph 0034-0035; 0038-0039; 0041-0042; 0044-0045; 0047, (2020/12/30)
The invention discloses an improved tofacitinib synthesis method and an impurity preparation method. By controlling pH value of the reaction liquid, the impurity type A is decomposed into the compound II, formic acid in the reaction liquid is easily removed, and the reaction yield and the tofacitinib quality are effectively improved. , The invention also provides a synthetic method of the impurity type A, which can be used for synthesizing the impurity type A through the method and detecting and controlling the quality of the tofacitinib. (by machine translation)
PROCESSES FOR PREPARING (3R,4R)-1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE OR A SALT THEREOF AND PROCESSES FOR PREPARING TOFACITINIB USING THE SAME
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Paragraph 119-123, (2020/10/20)
The present invention provides a novel process for preparing (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine or a salt thereof, which is an intermediate useful for the preparation of tofacitinib. The present invention also provides a novel intermediate used in the process, i.e., isopropanol solvate of methyl ((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)carbamate dibenzoyl-L-tartrate. The present invention also provides a novel intermediate, having excellent stability, useful for the preparation of tofacitinib, i.e., (3R,4R)-1-benzyl-N,4-dimethylpiperidin-3-amine acetate. In addition, the present invention provides a process for preparing tofacitinib or a pharmaceutically acceptable salt thereof using the process.
Preparation method of tofacitinib citrate
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Page/Page column 8; 9; 10; 11; 12; 13, (2020/02/14)
The invention relates to the field of medicine synthesis, and particularly discloses a preparation method of tofacitinib citrate. The preparation method comprises the following steps: S1, dissolving acompound SM1, a compound SM2 and an alkaline reagent in a solvent A, and performing a reaction to obtain a first compound; S2, taking and mixing a catalyst, a solvent B and the first compound, introducing hydrogen, and carrying out a catalytic hydrogenation reaction to obtain a second compound; S3, taking and mixing active anhydride, a solvent C and the second compound, and carrying out an acylation reaction to obtain a third compound, wherein R in the active anhydride comprises an alkyl group or an aryl group; and S4, taking and mixing citric acid, a solvent D and the third compound, and carrying out a salt-forming reaction to obtain a compound T that is the tofacitinib citrate. The preparation method has the advantages of easily available initial raw materials, no use of complex or toxic compounds, short synthesis process route, simple and convenient reaction operation of each step, high total yield and high productivity, and is suitable for large-scale industrial production.