A novel preparation method of epidermal growth factor receptor (EGFR) inhibitor neratinib

A technology of epidermal growth factor and neratinib, applied in the field of organic synthesis, can solve the problems of poor solubility of intermediates, large amount of solvent and high production cost
CN105461689BActive Publication Date: 2018-12-04SHANGHAI STEPPHARM CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
SHANGHAI STEPPHARM CO LTD
Publication Date
2018-12-04

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Abstract

The invention relates to a preparation method of an epidermal growth factor receptor (EGFR) inhibitor neratinib. The method is characterized in that 6-[(E)-4-(dimethylamino)-2-butenylamido]-7-ethoxy-4-chloro-3-quinolylmethylnitrile (I) continuously reacts with 2-chloro-3-aminophenol (II) and dichloromethylpyridine hydrochloride (III) to temporarily obtain an intermediate (E)-N-{4-[3-chloro-4-hydroxyanilino]3-cyno-5-ethoxy-6-quinolyl}-4-dimethylamino-2-butenylamide (IV) in order to finally obtain neratinib. The preparation method adopts a continuous reaction process, and dichloromethylpyridine hydrochloride (III) is a catalyst in the first stage of the continuous reaction and is a reaction reagent in the second stage of the continuous reaction, so the method has the advantages of simple and easily available raw materials, high yield, mild reaction conditions, extremely small amount of a generated waste liquid, and high facilitation of industrial production of the above raw medicine.
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Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a preparation method of an epidermal growth factor receptor (EGFR) inhibitor (neratinib). Background technique

[0002] An epidermal growth factor receptor (EGFR) inhibitor (neratinib), an irreversible EGFR inhibitor developed by Wyeth Pharmaceuticals, a subsidiary of Pfizer, can selectively inhibit the EGFR family HER-1 and HER-2 are useful in the treatment of cancers, especially those cancers affected by epidermal growth factor receptor family kinases, including but not limited to, pancreatic cancer, melanoma, lymphatic carcinoma, parotid tumor , Barrett's esophagus, esophageal cancer, head and neck cancer, ovarian cancer, breast cancer, epithelioid tumor, cancer of major organs such as kidney, bladder, larynx, stomach and lung, colon polyps and colorectal cancer, and prostate cancer.

[0003] Existing (neratinib) preparation routes mainly contain two: Route 1 uses 3-cyano-6-a...

Claims

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