- Preparation method of quinazolinyl butylene amide compound
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The invention discloses a preparation method of a quinazolinyl butylene amide compound, which effectively reduces the generation of impurities in the synthesis process by selecting a proper mixed alkali system and using a mixture of 1, 5-diaza-bicyclo [4.3. 0] nonyl-5-ene and potassium hydroxide, avoids the additional generation of degraded impurities in the medicine storage process, and accurate control over impurity generation and degradation is achieved.
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Paragraph 0045; 0050; 0053; 0058; 0060; 0065; 0067; 0072
(2021/07/17)
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- Arab league law for nepal preparation method of the compound
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The invention provides a novel preparation method of an afatinib compound. Raw materials and reagents used in the preparation method have the advantages of low cost, stable chemical property and convenience in long-term storage and the content of an impurity cis-isomer in the prepared afatinib compound is very low.
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- Preparation method of afatinib maleate
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The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of afatinib maleate. The preparation method of the afatinib maleate comprises thefollowing steps: reacting N4-(3-chloro-4-fluorophenyl)-
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- Novel afatinib dimaleate crystal form and preparation method and application thereof
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The invention relates to a novel afatinib dimaleate crystal form and a preparation method and application thereof. The novel crystal form improves the physical and chemical properties of an existing crystal form of the afatinib dimaleate and has good flui
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Paragraph 0031-0040
(2019/06/30)
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- The second maleic acid arab league law for nepal preparation method
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The invention relates to a preparation method of afatinib dimaleate, and concretely relates to a preparation method of an antitumor medicine afatinib dimaleate. The method comprises the following steps: carrying out a substitution reaction on 6-amino-7-fl
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Paragraph 0037-0041
(2019/05/15)
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- PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF
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The present invention relates to an improved process for the preparation of N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethyl amino)-(2E)-2-butenamide (2Z)-2-butenedioate (1:2) represented by the following structural formula:
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- Preparation method of afatinib and maleate thereof
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The invention belongs to the technical field of synthesis of compounds, and relates to a preparation method of afatinib and maleate thereof. The preparation method comprises the following steps: in the presence of a first organic solvent, adopting N-4-[(3-chloro-4-fluorophenyl)]-7-{[(3S)-tetrahydrofuran-3-group]oxo}-4,6-quinazoline diamine as a raw material to have the acylation reaction with (E)-4-dimethyl amino crotonate hydrochloride to obtain an acylation reaction solution under the effect of thionyl chloride, water and alkaline water are added into the acylation reaction solution, the water phase is extracted by virtue of butyl acetate, an organic phase is collected, after the organic phase is washed, the organic phase is directly stirred and precipitated to obtain an afatinib crude product, then the afatinib crude product is refined to obtain a competitive product, and the competitive product reacts with maleic acid to obtain maleic acid afatinib. The method has the characteristics of being high in product yield, high in purity, low in impurity content, mild in reaction conditions, simple in operation, suitable for industrialized production and the like.
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Paragraph 0045-0050
(2018/09/08)
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- Polymorphic Forms of Afatinib Dimaleate
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The present disclosure relates to amorphous and crystalline forms of 2-butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethyl amino)-,(2E)-, (2Z)-2-butenedioate (1:2) (afatinib dimaleate). The prese
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Paragraph 0212; 0213-0218; 0221-0228; 0231; 0232; 0234-0243
(2018/02/28)
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- PHARMACEUTICAL COMPOSITIONS COMPRISING AFATINIB
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The present invention relates to a tablet comprising Afatinib or a pharmaceutically acceptable salt thereof, wherein the tablet is obtained by direct compression. The present invention further relates to a process for manufacturing a tablet of the invention as well as the use of the tablet of the invention.
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Page/Page column 27; 28; 29; 30; 31
(2017/03/14)
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- POLYMORPHIC FORMS OF AFATINIB DIMALEATE
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The present disclosure relates to amorphous and crystalline forms of 2-butenamide, N-[4- [(3-chloro-4-fluorophenyl)amino]7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-5 (dimethyl amino)-,(2E)-, (2Z)-2-butenedioate (1:2) (afatinib dimaleate). The pr
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Page/Page column 19
(2017/06/24)
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- POLYMORPHS AND PROCESS FOR THE PREPARATION OF QUINAZOLINYL DERIVATIVES
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The present invention relates to Quinazolinyl derivatives polymorph, process and composition thereof. (I)
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Page/Page column 16
(2016/10/31)
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- POLYMORPHIC FORMS OF AFATINIB FREE BASE AND AFATINIB DIMALEATE
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The present invention relates to crystalline forms of Afatinib and its dimaleate salt. The present invention also relates to processes for the preparation of crystalline forms of Afatinib and its dimaleate salt. The present invention further relates to pharmaceutical compositions of such crystalline forms of Afatinib dimaleate and use thereof in the treatment of a patient in need thereof.
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Page/Page column 33; 34; 35; 36; 37; 38
(2016/12/26)
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- Crystalline Forms of Afatinib Monomaleate, Preparation Methods and Pharmaceutical Compositions Thereof
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The present invention relates to the novel solid forms of Afatinib monomaleate and preparation methods thereof; the solid forms of Afatinib monomaleate of the present invention have many improved properties as compared to the known crystalline form of Afatinib salt; and the present invention also relates to pharmaceutical compositions containing the novel solid forms of Afatinib monomaleate as well as the uses thereof for treating terminal non-small cell lung cancer (NSCLS) and HER2 positive advanced breast cancer.
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Paragraph 0074-0076
(2016/08/17)
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- High-selectivity method for preparing afatinib dimaleate
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The invention relates to a high-selectivity method for preparing afatinib dimaleate. The method comprises the following steps: (1) subjecting N4-(3-chloro-4-fluorophenyl)-7-[[(3S)- tetrahydro-3-furanyl] oxy] -4,6-quinazolinediamine as a starting raw material and diisopropylphosphoric acid to a condensation reaction; (2) subjecting the product of step 1 and 2--dimethylamino-1-sodium hydroxysulphonate to a Horner-Wadsworth-Emmons reaction; (3) subjecting the product of step 2 and maleic acid to a salt formation reaction to obtain afatinib dimaleate. The product provided by the invention has very few cis-isomer, and individual impurities are all controlled below 0.1%, the quality is good, and method is suitable for preparing finished products in large quantity and meeting the requirements of medicinal active pharmaceutical ingredients specified by ICH.
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- CRYSTALLINE FORM OF AFATINIB DIMALEATE
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The present invention provides a crystalline Form I of afatinib dimaleate, its process for preparation and pharmaceutical composition thereof, and its use in the treatment of metastatic non-small cell lung cancer.
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Page/Page column 5; 6
(2016/04/26)
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- CRYSTALLINE FORMS OF AFATINIB DI-MALEATE
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The present disclosure encompasses crystalline forms of Afatininb di-maleate and methods of their use.
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- CRYSTALLINE FORMS OF AFATINIB DI-MALEATE
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Crystalline forms of Afatinib di-maleate are described in the present application and processes for their preparation. The present invention also includes pharmaceutical compositions of such crystalline forms of Afatinib di-maleate, methods of their preparation and the use thereof hi the treatment of a patient in need thereof. The present invention also describes preparing Afatinib free base and salts of Afatinib, other than Afatibin di-maleate, and solid forms thereof.
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Page/Page column 13; 14
(2013/04/24)
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- NOVEL SALTS AND POLYMORPHIC FORMS OF AFATINIB
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Afatinib salts and crystalline forms thereof are described in the present application and processes for their preparation. Crystalline forms of Afatinib are also described in the present application and processes for their preparation. The present invention also includes pharmaceutical compositions of such Afatinib salts and crystalline forms thereof or crystalline forms of Afatinib, methods of their preparation and the use thereof in the treatment of a patient in need thereof.
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Page/Page column 53-54
(2012/09/22)
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- Process for preparing amino crotonyl compounds
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The invention relates to an improved process for preparing 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylam ino)-1 -oxo-2-buten-1 -yl]am ino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline and related aminocrotonyl compounds and the preparation of a suitable salt of 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1 -oxo-2-buten-1 -yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline for use as a pharmaceutically active substance.
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Page/Page column 6-7
(2010/02/11)
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