- An environment friendly process for the preparation of Lapatinib Ditosylate of Formula 1(b)
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The present invention relates to a process for the preparation of Lapatinib Ditosylate of formula 1(b). More particularly, the present invention relates to environment friendly process that involves green chemistry in preparation of Lapatinib Ditosylate of formula 1(b). The said process is economically and commercially viable as initial 2 stages of processes use water as solvent avoiding hazardous reagent or solvent during the preparation of Lapatinib Ditosylate of formula 1(b).
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- IMPROVED PROCESS FOR THE PREPARATION OF LAPATINIB BASE AND IT'S ANHYDROUS DITOSYLATE SALT
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The present invention relates to an improved, high yielding and industrially viable process for the preparation of high pure Lapatinib of formula (1). The present invention involves simple crystallization techniques avoiding column chromatographic techniques and the process conditions can be easily adopted for scale-up studies.
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Paragraph 11
(2020/07/15)
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- A high-purity paratoluene sulfonic acid lapatinib a preparation method of water composition
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The invention relates to a high-purity paratoluene sulfonic acid lapatinib a water composition of the preparation method, the method comprises the following steps: (1) the compound II with compound III under alkaline conditions, the catalyst under the action of the Suzuki coupling to obtain compound IV; (2) the compound IV with a compound V in weakly alkaline conditions, in the catalyst under the action of the joint, by the three-b acyl sodium borohydride reduction, paratoluene sulfonic acid to form the salt to obtain compound VI; (3) the compound VI with the recrystallization to obtain compound I, is the second-to-toluene sulfonic acid lapatinib a hydrate. The programme provides at least to a certain extent one of the solve the above technical problems or at least provide a useful commercial choice. To avoid the use of toxicity is relatively high, the environmentally harmful solvent or reagent, the reaction route is operating time is short, the reaction system is stable, the purification process is simple, the product purity is higher, it is suitable for industrial production.
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Paragraph 0020
(2019/04/04)
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- Method for synthesizing lapatinib or intermediate 5-(4-hydroxy quinazoline)-furan-2-formaldehyde of lapatinib
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The invention relates to a method for synthesizing lapatinib or intermediate 5-(4-hydroxy quinazoline)-furan-2-formaldehyde of lapatinib. The method for synthesizing the intermediate comprises steps as follows: 4-hydroxy-6-nitro quinazoline reacts with hydrazine hydrate in a solvent in the presence of a catalytic amount of catalyst, and 4-hydroxy-6-amino quinazoline is prepared; 4-hydroxy-6-amino quinazoline reacts with furaldehyde in the solvent in presence of acid, sodium nitrite and a catalytic amount of catalyst, and the intermediate is prepared. The invention further relates to a method for synthesizing lapatinib and/or a lapatinib salt, a lapatinib intermediate and/or a pharmaceutically acceptable salt of the intermediate. The method is performed by using the intermediate synthesized with the method. The method has the advantages that steps are simplified, agents are cheap, available and high in utilization rate, heavy metal pollution is avoided, the reaction condition/operation requirement is lower and/or the yield is high and the like.
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Paragraph 0034; 0051; 0052; 0053
(2017/03/22)
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- Method for synthesizing lapatinib or intermediate thereof
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The invention relates to a method for synthesizing lapatinib or an intermediate thereof. The method for synthesizing the intermediate comprises the steps as follows: under the condition that a catalytic quantity of a catalyst exists in a solvent, 4-amino-5-(4-(3-chloro-4-(3-fluorobenzyloxy) phenylamino)-quinazoline reacts with furfural for preparation of 5-(4-(3-chloro-4-(3-fluorobenzyloxy) phenylamino)-quinazoline-6-yl)furyl-2-carboxaldehyde hydrochloride, and the intermediate is prepared. The invention further relates to a method for synthesizing lapatinib and/or salt of lapatinib, the intermediate of lapatinib and/or pharmaceutically acceptable salt of the intermediate, and the method is performed with the intermediate which is synthesized by the previous method. The method has the advantages that steps are simplified, a reagent is cheap, available and high in use ratio, pollution from heavy metal is avoided, and requirements for reaction conditions/operation are relatively low and/or the yield is high.
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- Preparing method of lapatinib and preparing method of lapatinib ditosylate
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The invention provides a preparing method of lapatinib. The preparing method includes the steps that under nitrogen protection, a compound in the formula (IV) (please see the specification), 5-formyl-2-furanboronic acid, organic base or inorganic base, tetrahydrofuran and ethanol are mixed, the temperature is increased to 60-70 DEG C, stirring is carried out, a palladium catalyst is added, and a reaction is carried out under the temperature control condition; after the mixture is completely reacted, filtering, filter liquor cooling, water dripping, stirring, filtering and drying are carried out, the obtained product and 2-(methylsulfonyl) ethylamine hydrochloride are further reacted under the condition of existing of glacial acetic acid, then NaBH(OAC)3 is added for a reduction reaction, and lapatinib is obtained. The invention further provides a preparing method of lapatinib ditosylate. The preparing method includes the steps that a tetrahydrofuran solution of p-toluenesulfonic acid-monohydrate is dropwise added into the lapatinib or a solution obtained before concentrating, and the lapatinib ditosylate is obtained. The methods are convenient to operate, small in solvent dosage, low in production cost, small in environment pollution, high in product yield and purity and more suitable for industrial production.
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- Lapatinib process for the preparation of intermediates
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The invention discloses a preparation method of a Tykerb intermediate. The preparation method of the Tykerb intermediate 1 comprises the following steps: (1) performing a nucleophilic substitute reaction on a compound as shown in a formula 3 and a compound as shown in a formula 4 under the effect of a catalyst in an organic solvent, wherein X is chlorine or bromine, M is sodium, potassium or zinc, and n is equal to 1 or 2; and (2) enabling a compound 2 obtained in the step (1) to react in a hydrogen chloride solution. According to the preparation method of the Tykerb intermediate 2, the nucleophilic substitute reaction is carried out on the compound as shown in the formula 3 and the compound as shown in the formula 4 under the effect of the catalyst in the organic solvent. The preparation method disclosed by the invention is simple to operate, the raw materials are cheap and easy to obtain, no environment pollution factor is caused, and the method is suitable for large-scale production in industry.
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Paragraph 0027; 0028
(2017/01/17)
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- CANCER TREATMENT METHOD
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A method of treating cancer is described including administration of a 4-quinazolineamine and at least one other anti-neoplastic agent as well as a pharmaceutical combination including the 4-quinazolineamines.
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Paragraph 0163-0164
(2016/03/12)
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- EFFICIENT PROCESS FOR THE PREPARATION OF LAPATINIB AND SALTS THEREOF BY MEANS OF NEW INTERMEDIATES
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The present invention refers to a new efficient process for the synthesis of the active pharmaceutical ingredient Lapatinib and salts thereof. In particular, the present synthesis is carried out employing new intermediates in which the amine function is protected by a group cleavable in basic milieu that provides a higher overall yield of the synthesis process.
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- Methods for detecting and reducing impurities of Lapatinib and salts thereof
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Impurities of lapatinib such as N-{3-chloro-4-[(2-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine compound of formula (I) or a salt thereof: and analytical methods for identifying and quantifying such impurities of Lapatinib and salts thereof are provided. Also provided is Lapatinib containing less than about 0.05 percent of this and related impurities and methods for preparing such pure forms of Lapatinib.
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Page/Page column 21-22
(2015/02/18)
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- CO-CRYSTALS OF LAPATINIB MONOACID SALTS
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The present invention refers to co-crystals of monoacid salts of the pharmaceutical active ingredient named Lapatinib and to processes for the preparation thereof and medical uses.
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Paragraph 00117; 00118; 00119; 0020; 00121; 00122
(2015/11/10)
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- PROCESS FOR THE PREPARATION OF LAPATINIB
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Present process relates to an improved and commercial process for the preparation of lapatinib of formula-I or its pharmaceutically acceptable p-toluenesulfonate salt involving novel intermediates of formulae-XVII, XVIII, and XIX. Present process utilizes Meerwein reaction as a key step in the aryl C-C bond formation step avoiding costly boronate coupling chemistry used in the conventional synthesis of lapatinib.
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- NOVEL INTERMEDIATES AND PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention discloses novel intermediates and processes for the synthesis of Lapatinib and its pharmaceutically acceptable salts thereof.
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- A PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS DITOSYLATE SALT
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There is provided processes for preparing Lapatinib and pharmaceutically acceptable salts thereof by the reductive amination of the aldehyde of Formula II by treatment with 2-methanesulphonylethylamine followed by catalytic hydrogenation in the presence of a suitable hydrogenation catalyst.
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Page/Page column 10
(2012/07/13)
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- METHODS FOR THE PREPARATION OF LAPATINIB AND THE SALTS THEREOF
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Methods for the synthesis of the pharmaceutically active ingredient Lapatinib and the salts thereof are provided. In particular, such methods utilize intermediates in which the hydroxyl function is protected by a tetrahydropyranyl group providing greater solubility of the intermediates in common organic solvents.
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- Impurity of lapatinib and salts thereof
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The present invention regards an impurity of lapatinib, N-{3-chloro-4-[(2-fluorobynzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl] quinazoline-4-amine compound of formula (I) or a salt thereof: the analytical methods for identifying it and quantifying it in Lapatinib and salts thereof. The invention also regards Lapatinib comprising less than 0.05 percent of this impurity and the relative method of preparation.
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Page/Page column 13; 14
(2012/09/10)
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- Process for the preparation of lapatinib and the salts thereof
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The present invention refers to a new process for the synthesis of the pharmaceutical active ingredient Lapatinib and the salts thereof. In particular, the present synthesis is performed using intermediates in which the hydroxyl function is protected by the tetrahydropyranyl group hence entailing greater solubility of the intermediates in the common organic solvents.
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- SALTS OF LAPATINIB
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The present invention provides novel dioxalate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides novel monobesylate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention further provides a process for the preparation of monohydrate form of lapatinib ditosylate. The present invention further provides a process for the preparation of anhydrous form of lapatinib ditosylate.
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- NOVEL PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved and novel process for the preparation of high purity crystalline base of Lapatinib of formula-(1) having chemical name N-{3-chloro-4-[(3-fluorobenzyloxy]phenyl}-6-[5-({[2-(methanesulfonyl)ethyl]amino}methyl]-2-furyl]-4-quin-azolinamine and its pharmaceutically acceptable salts. The present invention further relates to intermediates according to formula (8) and formula (9) used in this process
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- A NEW PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved and new process for the preparation of high purity crystalline base of Lapatinib of formula (1) having chemical name N-{3-chloro-4-[(3-fluorobenzyloxy]phenyl}-6-[5-({[2-(methanesulfonyl) ethyl]amino}methyl]-2-furyl]-4-quin -azolinamine and its pharmaceutically acceptable salts.
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- PROCESS AND INTERMEDIATES FOR PREPARING LAPATINIB
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Provided are a process for preparing lapatinib and its pharmaceutically acceptable salt by use of new intermediates, and a process for obtaining a pharmaceutical form of lapatinib ditosylate monohydrate.
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Page/Page column 16-17
(2011/10/13)
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- POLYMORPHIC FORMS OF LAPATINIB DITOSYLATE AND PROCESSES FOR THEIR PREPARATION
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There is provided a crystalline form of Lapatinib, termed APO-I, and methods for making APO-I. There is also provided a crystalline solvate form of Lapatinib, termed APO-II, and methods for making APO-II.
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Page/Page column 15; 16
(2011/11/06)
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- LAPATINIB INTERMEDIATES
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The invention provides lapatinib intermediates and improved processes for preparing lapatinib intermediates. The invention also provides processes for preparing lapatinib base and lapatinib ditosylate.
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Page/Page column 23
(2010/04/03)
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- A NOVEL PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
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The present invention relates to an improved and novel process for the preparation of high purity crystalline base of Lapatinib of formula-(l) having chemical name N-{3-chloro-4-[(3- fluorobenzyloxy]phenyl}-6-[5-({[2-(methanesuIfonyl) ethyl]amino}methyl]-2-furyl]-4-quin - azolinamine and its pharmaceutically acceptable salts. The present invention further relates to intermediates according to formula (8) and formula (9) used in this process
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Page/Page column 17
(2010/06/17)
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- FORMS OF LAPATINIB COMPOUNDS AND PROCESSES FOR THE PREPARATION THEREOF
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The present invention provides novel crystalline and amorphous lapatinib compounds and processes for preparing them
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Page/Page column 7
(2010/04/30)
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- QUINAZOLINE DITOSYLATE ANHYDRATE FORMS
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Crystalline forms of anhydrate ditosylate salts of 4-quinazolineamines are described as well as methods of using the same in the treatment of disorders characterized by aberrant erbB family PTK activity.
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Page/Page column 24
(2009/07/18)
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- FORMS OF LAPATINIB DITOSYLATE AND PROCESSES FOR PREPARATION THEREOF
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The present invention provides novel polymorphs of lapatinib ditosylate, processes for preparing them, and pharmaceutical compositions comprising one or more of these polymorphs.
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Page/Page column 9
(2009/12/04)
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- 4-Aminoquinazoline derivatives and methods of use thereof
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This invention relates to novel 4-aminoquinazolines, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering inhibitors of the EGFR and HER-2.
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Page/Page column 14-16
(2008/06/13)
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering an erb family inhibitor and an IGF-1R inhibitor to a mammal suffering from a cancer.
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional EGFR and/or erbB-2 inhibitor. In particular, the method relates to methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional EGFR and/or erbB-2 inhibitor.
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Page/Page column 24-25
(2010/10/20)
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- CANCER TREATMENT METHOD
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A method of treating cancer is described including administration of a pyrimidine derivative and a quinazoline derivative as well as a pharmaceutical composition including the same.
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound.
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and pharmaceutical compositions containing the same. In particular, the method relates to a methods of treating cancers which are mediated by the tyrosine kinases EGFR and/or erbB2 by administration of N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methanesulphonyl) ethyl]amino} methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof.
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering an erb family inhibitor and a PI3K and/or Akt inhibitor to a mammal suffering from a cancer.
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Page/Page column 69-70
(2010/02/11)
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