Method for preparing lapatinib intermediate

A technology of latratinib and intermediates, which is applied in the field of preparation of latratinib intermediates, can solve problems such as unfavorable industrial production, reduced atom economy of preparation process, numerous steps, etc., and achieves improved reaction yield and operational feasibility. controllability, reduction of precious metal catalysts and other expensive reagents, and the effect of promoting development
CN107445879AActive Publication Date: 2017-12-08SUZHOU LIXIN PHARMA
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
SUZHOU LIXIN PHARMA
Publication Date
2017-12-08

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Abstract

The invention discloses a method for preparing a lapatinib intermediate (R)-2-(2,5-difluorophenyl)tetrahydropyrrolidine. The method comprises the following steps: by taking taking chiral induced reagent (7aR,10R,12S)-10-(1-benzotriazole)-12-phenyl-7a,8,9,10-tetrahydro-12H-naphthol[1,2-e]pyrrolo[2,1-b][1,3]oxazine and a Grignard reagent 2,5-difluorophenyl magnesium bromide as raw materials, performing a substitution reaction, a reduction reaction and a debenzylation reaction to prepare the lapatinib intermediate (R)-2-(2,5-difluorophenyl)tetrahydropyrrolidine. Compared with the prior art, the method is simple in process, mild in condition, less in side reaction, low in cost and suitable for industrial production and can promote development of the bulk drug economic technology.
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Description

technical field

[0001] The invention belongs to the technical field of organic synthesis route design and preparation of raw materials and intermediates, and in particular relates to a preparation method of a latratinib intermediate. Background technique

[0002] Larotrectinib is a potent, oral, selective tropomyosin receptor kinase (TRKs) inhibitor developed by LoxoOncology, a biopharmaceutical company located in Stanford, USA. In May 2017, the US Food and Drug Administration (FDA) granted the experimental drug orphan drug status for the treatment of solid tumors carrying NTRK gene fusions.

[0003] The chemical name of latratinib is (S)-N-((R)-2-(2,5-difluorophenyl) tetrahydropyrrolidin-1-yl) pyrazol[1,5-a] Pyrimidin-3-yl-3-hydroxytetrahydropyrrolidine-1-carboxamide, its chemical structure is:

[0004]

[0005] The preparation method of latratinib has been reported. International patents WO2010 / 048314 and WO2016 / 077841 report the preparation method of latratinib, and ...

Claims

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