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Preparation method of PF06651600

A synthetic method and compound technology, applied in the field of medicine, can solve the problems of being unsuitable for large-scale production, inability to scale up, and high cost, and achieve good industrial application prospects, reduce dangerous operations, and have high controllability

Inactive Publication Date: 2021-07-16
JIANGSU ALICORN PHARMATECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The patented route has lengthy steps, two chiral chromatographic column separations, not only the yield is low, the cost is high, and it cannot be scaled up; the dry Pd / C catalyst used in catalytic hydrogenation is very dangerous and often cannot be completely reacted, and two rounds of hydrogenation desorption are required. Chlorine, obviously not suitable for large-scale production

Method used

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  • Preparation method of PF06651600
  • Preparation method of PF06651600
  • Preparation method of PF06651600

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Embodiment Construction

[0019] The present invention is specifically described below by the examples, it is necessary to point out again that the following examples are only used to further illustrate the present invention, and can not be interpreted as limiting the protection scope of the present invention.

[0020] Synthesis of N-((3R,6S)-1-benzyl-6-methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (4)

[0021]

[0022] In a 5L autoclave, add (3R,6S)-1-benzyl-6-methylpiperidin-3-amine (170.00g, 832.04mmol, 1.0eq), 4-chloropyrrolo[2,3- D] pyrimidine (140.55g, 915.24mmol, 1.0eq), diisopropylethylamine (287.60g, 2.50mol, 3.0eq), add n-butanol (1700ml) and heat up to 140°C and stir overnight, TLC monitoring (dichloro Methane / methanol=20:1), the reaction was complete, the heating was stopped, and the temperature was naturally cooled to room temperature. Ethyl acetate (3500ml) and water (3500ml) were added, stirred and separated, and the organic phase was concentrated under reduced pressure to...

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Abstract

The invention provides a preparation method of PF06651600, and particularly relates to a method for preparing a target product PF06651600 by taking a pure enantiomer (3R,6S)-1-benzyl-6-methyl piperidine-3-amine as an initial raw material and carrying out reaction with 4-chloropyrrolo [2,3-D] pyrimidine, hydrogenation debenzylation and reaction with acryloyl chloride. The enantiomer is used as a raw material, expensive chiral chromatographic separation in the later period is avoided, the reaction condition is mild, the controllability is high, and the preparation method has a good industrial application prospect.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to a method for preparing PF06651600. Background technique [0002] PF-06651600(1) is a highly selective and orally bioavailable Janus kinase 3 (JAK3) inhibitor developed by Pfizer, representing a potential immunomodulatory therapy. Due to its good efficacy, safety and ADME properties, this JAk3-specific covalent inhibitor has been used in the treatment of alopecia areata, rheumatoid arthritis, Crohn's disease and ulcerative colitis. On September 5, 2018, the FDA granted PF-06651600 a "Breakthrough Therapy" designation for the treatment of alopecia areata, supported by positive results from a Phase 2 study. The preparation method of this compound is disclosed in the patent WO2015 / 083028, as follows. [0003] [0004] [0005] The patented route has lengthy steps, two chiral chromatographic column separations, not only the yield is low, the cost is high, and it cannot be scale...

Claims

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Application Information

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IPC IPC(8): C07D487/04
CPCC07D487/04C07B2200/07A61P1/00A61K31/4375
Inventor 陈磊吴心宇陆平波
Owner JIANGSU ALICORN PHARMATECH CO LTD