New synthesis methods of JCK inhibitor baricitinib and intermediate thereof

A technology of baricitinib and synthetic methods, applied in the field of medicine and chemical industry, can solve the problems of expensive 3-hydroxyazetidine starting raw materials, unsatisfactory product yield and purity, poor stability of acetonitrile, etc., and achieve improvement The effect of route efficiency and atom economy, simplified separation and purification process, and simple operation
CN106946917AActive Publication Date: 2017-07-14HANGZHOU CHEMINSPIRE TECH CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
HANGZHOU CHEMINSPIRE TECH CO LTD
Publication Date
2017-07-14

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Abstract

The present invention provides a new synthesis method of a baricitinib compound 11. According to the present invention, by using a compound 1 as a staring raw material, the amino group is protected by directly using ethanesulfonyl chloride, and direct cyclization is directly performed by using the effect of an alkali to obtain a key intermediate compound 3 so as to avoid the use of other protection groups and substantially improve the route efficiency and the atomic economy; during the compound 5 preparation, a Wittig reaction is performed by using triphenylphosphine acetonitrile so as to avoid the use of strong alkali and improve the reaction yield; the completely-new neopentyl glycol borate derivative compound 8 has good stability and good crystallinity so as to simplify the separation and purification process; and the route is simple to operate and has the high yield, the purity of the obtained product is high, and the synthesis method is suitable for amplification production. The formulas 1-11 are defined in the specification.
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Description

technical field

[0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a new intermediate of rheumatoid arthritis drug baricitinib, a synthesis method thereof, and a method for preparing baricitinib by using the intermediate. Background technique

[0002] Baricitinib is a selective oral JAK1 / JAK2 inhibitor jointly developed by Eli Lilly and Incyte Pharmaceuticals, which can inhibit the intracellular signaling of various inflammatory cytokines such as IL-6 and IL-23 , for the treatment of autoimmune diseases and related inflammations, such as rheumatoid arthritis, psoriasis and diabetic nephropathy. EMA has approved baricitinib as a single agent or in combination with methotrexate on February 13, 2017, for moderate to severe activity inadequately responded to or intolerant to one or more disease-modifying antirheumatic drug (DMARD) therapy Treatment of adult patients with rheumatoid arthritis (RA).

[0003] Baricitinib chem...

Claims

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