Method for preparing Afatinib and intermediate thereof
AssigneeSuzhou Miracpharma Technology Co., Ltd.
InventorXuenong Xu
Life of this patent
Estimating the term…
Abstract
Revealed in the present invention is a method for preparing Afatinib (I): using 2-nitrile-4-[4-(N,N-dimethylamino-1-oxo-2-buten-l-yl]amino-5-[(S)-(tetrahydrofuran-3-yl)oxy]aniline (II) and 4-fluoro-3-chloroaniline (III) as starting materials, and respectively performing a condensation and cyclization reaction with N,N-dimethylformamide dimethylacetal (IV) to prepare Afatinib (I), wherein the method significantly reduces the manufacturing steps of Afatinib and greatly lower the costs. In addition, also provided in the present invention is a method for preparing an intermediate of Afatinib, wherein the method has a stable process, uses readily available starting materials, has a low cost, and all the reactions are classic reactions, suitable for meeting amplification requirements in the industry.
Claims8
A method for preparing Afatinib (4-[(3-chloro-4-fluorophenyl) amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl] amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy] quinazoline, I),
- comprising the following steps:
- 1) a condensation reaction of N,N-dimethylformamide dimethyl acetal (IV) and 2-nitrile-4-[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl] amino-5-[(S)-(tetrahydrofuran-3-yl)oxy] aniline (II) to product an intermediate N′-[5-nitrile-4-[4-(N,N-dimethylmethylene)amino]-2-[(S)-(tetrahydrofuran-3-yl) oxy] phenyl]-4-(N,N-dimethylformamide)-2-butenamide (V);
- and
- 2) a cyclization reaction of the intermediate (V) and 4-fluoro-3-chloroaniline (III) to prepare Afatinib (I).
Dependencies are inferred from the claim text.