Entironment-friendly preparation of sorafenib intermediate

An environmentally friendly and intermediate technology, applied in the field of preparation of sorafenib intermediates, can solve environmental pollution and other problems, and achieve the effect of no waste gas emission and easy purification

Active Publication Date: 2008-11-12
SHANGHAI HWASUN LIFE SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The technical problem to be solved by this invention is to provide new N-methyl-(4-chloro-2-pyridyl) formamide (structural formula as shown i

Method used

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  • Entironment-friendly preparation of sorafenib intermediate
  • Entironment-friendly preparation of sorafenib intermediate
  • Entironment-friendly preparation of sorafenib intermediate

Examples

Experimental program
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Example Embodiment

[0028] The preparation of embodiment N-methyl-(4-chloro-2-pyridyl) formamide

[0029] 1. Dissolve 4-chloropyridine hydrochloride in an appropriate amount of formamide, and slowly add 1.5 equivalents of hydrogen peroxide and 1.5 equivalents of ferrous sulfate heptahydrate at 10-15°C [temperature range 0°C-100°C] (both added at the same time , independently). After the reaction, excess formamide was distilled off, the residue was extracted with chloroform, washed with water and concentrated to dryness to obtain 4-chloropyridine-2-carboxamide.

[0030] 2. Dissolve 1.0 mol of 4-chloropyridine-2-carboxamide in an appropriate amount of anhydrous methanol, slowly add 1.02 mol of concentrated sulfuric acid dropwise, heat up and reflux until all raw materials disappear [reaction temperature 20-80°C]. Part of the methanol was recovered, and the reaction liquid was slowly added dropwise to the aqueous sodium bicarbonate / ethyl acetate two-phase system (sodium bicarbonate 1.2 mol) under s...

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Abstract

The invention belongs to pharmaceutical chemistry technical field, and in particular relates to a method for preparing a sorafenib intermediate. The invention discloses a method for preparing sorafenib intermediate N-methyl-(4-chlorine-2-pyridyl) formamide. The method is characterized in comprising three steps of amidation, esterification of methyl alcohol and ammonolysis of methylamine. The synthesis method provided by the invention has the advantages of easier product purification, no waste gas discharged in the production process, and being more environment-friendly, compared with the prior synthesis method of thionyl chloride.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of a Sorafenib intermediate. Background technique [0002] Sorafenib (sorafenib), chemical name 4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureide]-phenoxy}-pyridine-2-carboxylic acid Methylamine, the structural formula is shown in formula I. Sorafenib adopts a "multi-target" approach to attack tumor cells, and has effects on Raf-1 kinase, B-Raf, vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, Fms-like tyrosine kinase-3 ( Flt-3) and stem cell growth factor (c-KIT) both have inhibitory effects. On the one hand, it can reduce tumor cell proliferation through upstream inhibition of receptor tyrosine kinases KIT and FLT-3, and downstream inhibition of serine-threonine kinase in the RAF / MEK / ERK pathway; on the other hand, through upstream inhibition of receptor Tyrosine kinases VEGFR and PDGFR, and...

Claims

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Application Information

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IPC IPC(8): C07D213/81
Inventor 刘新科
Owner SHANGHAI HWASUN LIFE SCI
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