- A high-purity malic acid lin's preparation method
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The invention relates to a high-purity malic acid lin's preparation method, the method comprises the following steps: (1) the formula II compound as a starting material, the use of 1 - ethyl - (3 - dimethyl amino propyl) carbonylamino-carbodiimide hydrochloride with 1 - hydroxy benzotriazole as the condensing agent, under certain temperature and N, N diethylethylenediamine reaction to obtain compound III; (2) in the step (1) the reaction solution, between the step (1) the resulting reactant with 5 - fluoro indole - 2 - one reaction at certain temperature, to obtain compound IV; (3) in the step (2) of the reaction solution, so that the step (1) the resulting reactant with L - malic acid reaction at certain temperature, to obtain compound I; providing at least to a certain extent one of the solve the above technical problems or at least provide a useful commercial choice. The reaction route is operating time is short, simple operation, reaction system is stable, higher product yield, purity of the product is relatively high, it is suitable for industrial production.
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- High-purity L-sunitinib malate preparation method
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The present invention discloses a high-purity L-sunitinib malate preparation method, which comprises the following reaction route defined in the specification, wherein the step a comprises that a B5 compound and 5-fluoroindol-2-one are subjected to an Aldol condensation reaction to obtain a sunitinib free base (B6 compound), the step b comprises that the B6 compound and L-malic acid are subjected to a salt forming reaction to obtain the L-sunitinib malate, and the step a and the step b are performed in a dark place. According to the present invention, the HPLC purity of the prepared L-sunitinib malate can achieve more than 99.8%, the single impurity content can be controlled at less than 0.1%, and the quality difficulty of the application of the L-sunitinib malate in the preparation is effectively solved.
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- PROCESS FOR THE PERPARATION OF SUNITINIB AND ITS ACID ADDITION SALTS THEREOF
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The present invention relates to an improved process for the preparation of Sunitinb. The process involves the activation of 5-((Z)-(5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3carboxylic acid to corresponding suitable carboxylic acid activating group. The present invention also relates to novel acid addition salts of Sunitinb and preparation thereof.
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- PROCESSES FOR THE PREPARATION OF 3-(PYRROL-2-YL)METHYLENE)-2-PYRROLONES USING 2-SILYLOXY-PYRROLES
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The present invention provides for synthetic processes for the making of substituted 3-((pyrrol-2-yl)methylene)-2-pyrrolones, including sunitinib. The present invention also provides for a process of crystallizing substantially pure sunitinib L-malate.
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- PROCESS FOR THE DIRECT PREPARATION OF MALIC ACID SALT OF SUNITINIB
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The present invention relates to a process for the direct preparation of malic acid salt of sunitinib.
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Paragraph 0014; 0015; 0016
(2013/05/22)
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- PROCESS FOR PREPARATION OF HIGH PURITY N- [2- (DIETHYLAMINE) ETHYL] - 5 - FORMYL - 2, 4 - DIMETHYL - 1H - PYRROLE - 3 - CARBOXYAMIDE
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The present invention relates to preparation of high purity N-[2- (diethylamine)ethyl]-5-formyl-2,4-dimethyl- 1 H-pyrrole-3-carboxyamide, comprising purification to obtain the product including less than 0.07% of desethyl derivative, N- [2-(ethylamine)ethyl]-5-formyl-2,4-dimethyl-lH-pyrrole-3-carboxyamide. N-[2- (diethylamine)ethyl]-5-formyl-2,4-dimethyl- 1 H-pyrrole-3-carboxyamide containing less than 0.07% of desethyl derivative is the valuable intermediate in the process for preparation of active pharmaceutical ingredient sunitinib.
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Page/Page column 12-13
(2013/11/18)
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- PROCESSES FOR THE PREPARATION OF 3-(PYRROL-2-YL)METHYLENE)-2-PYRROLONES USING 2-SILYLOXY-PYRROLES
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The present invention provides for synthetic processes for the making of substituted 3-(Pyrrol-2-yl)methylene)-2-pyrrolones, including sunitinib. The present invention also provides for a process of crystallizing substantially pure sunitinib L-malate.
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- PROCESS FOR THE PREPARATION OF HIGH PURITY SUNITINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALT
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The present invention relates to an improved process for the preparation of N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide—Sunitinib base of formula (I) and its pharmaceutically acceptable malate salt of formula (I(a)).
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- NOVEL PROCESS
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The present invention relates to novel processes for the preparation of sunitinib and salts thereof, in particular sunitinib (2S)-2-hydroxybutanedioate. The invention further relates to novel intermediates, their use in the preparation of sunitinib or salts thereof and to processes for the preparation of said intermediates. The invention also relates to compositions comprising sunitinib or its pharmaceutically acceptable salts.
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Page/Page column 31-33
(2011/11/01)
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- NOVEL PROCESS
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The present invention relates to an improved process for preparing acid addition salts of sunitinib, in particular sunitinib (2S)-2-hydroxybutanedioate (I). The invention also relates to compositions comprising sunitinib acid addition salts such as sunitinib (2S)-2- hydroxybutanedioate (I) and to the use of said compositions in the treatment of disease.
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- CRYSTALLINE FORMS OF L-MALIC ACID SALT OF SUNITINIB
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The present invention relates to crystalline forms of L-malic acid salt of sunitinib and its preparation. The crystalline forms of the present invention are designated as Form V and Form VI of L-malic acid salt of sunitinib. Formula (I).
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Page/Page column 7
(2011/08/21)
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- PROCESS FOR THE DIRECT PREPARATION OF MALIC ACID SALT OF SUNITINIB
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The present invention relates to a process for the direct preparation of malic acid salt of sunitinib.
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Page/Page column 4
(2011/10/03)
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- PROCESS FOR THE PREPARATION OF CRYSTALLINE FORMS OF SUNITINIB MALATE
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The present invention, relates to novel processes for the preparation of sunitinib malate formula (I), pharmaceutical compositions comprising said polymorph and the use of the said pharmaceutical compositions in the treatment of various forms of cancer.
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Page/Page column 9-10
(2011/10/31)
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- PROCESS FOR THE PREPARATION OF CRYSTALLINE FORM I OF L-MALIC ACID SALT OF SUNITINIB
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The present invention relates to a process for the preparation of crystalline Form I of the L-malic acid salt of sunitinib.
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Page/Page column 4
(2011/06/16)
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- NOVEL POLYMORPHS OF SUNITINIB MALATE
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The present invention provides a novel crystalline form of sunitinib malate, process for its preparation and to pharmaceutical composition containing it. The present invention also provides a process for preparation of sunitinib malate crystal form I. Thus, for example, sunitinib malate was added to water, the mixture was heated to 80 deg C. to obtain a clear solution and stirred for 30 minutes at 80 deg C., slowly cooled to room temperature and the solution was subjected to freeze drying at about ?90 deg C. for 8 hours to give sunitinib malate crystalline form III.
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Page/Page column 2
(2012/01/03)
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- PROCESSES FOR THE PREPARATION OF CRYSTALLINE FORMS OF SUNITINIB MALATE
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The present invention, relates to novel processes for the preparation of sunitinib malate formula (I), pharmaceutical compositions comprising said polymorph and the use of the said pharmaceutical compositions in the treatment of various forms of cancer.
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Page/Page column 28-29
(2010/04/03)
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- CRYSTALLINE FORMS OF A 3-PYRROLE SUBSTITUTED 2-INDOLINONE MALATE SALT
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Disclosed are crystalline polymorphic forms of the malic acid salt of (Z)-N-[2- (diethylamino)ethyl]-5-[(5-fluoro-l,2-dihydro-2-oxo-3H-indol-3-yliden)methyl]-2,4- dimethyl-1H-pyrrole-3-carboxamide, sunitinib malate, including crystalline Forms III, IV, V, VI and VII. Also disclosed are processes for preparing crystalline polymorphic forms of sunitinib malate and pharmaceutical compositions comprising sunitinib malate.
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Page/Page column 10
(2010/04/03)
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- NOVEL POLYMORPHS OF SUNITINIB MALATE
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The present invention provides a novel crystalline form of sunitinib malate, process for its preparation and to pharmaceutical composition containing it. The present invention also provides a process for preparation of sunitinib malate crystal form I. Thus, for example, sunitinib malate was added to water, the mixture was heated to 80 deg C to obtain a clear solution and stirred for 30 minutes at 80 deg C, slowly cooled to room temperature and the solution was subjected to freez drying at about -90 deg C for 8 hours to give sunitinib malate crystalline form III.
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Page/Page column 4
(2010/08/04)
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- Process For Preparing A 3-Pyrrole Substituted 2-Indolinone Malate Salt
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The invention relates to the malic acid salt of N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide, to the use thereof as an intermediate for preparing the malic acid salt of sunitinib, and to pharmaceutical compositions comprising said malic acid salt of sunitinib.
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Page/Page column 3-4
(2009/12/28)
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- PROCESS FOR THE PREPARATION OF HIGH PURITY SUNITINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALT
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The present invention relates to an improved process for the preparation of N- [2- (diethylamino)ethyl]-5-[(Z)-(5-fluoro- 1,2-dihydro-2-oxo-3H-indol-3-ylidine) methyl]- 2,4-dimethyl-1H-pyrrole-3-carboxamide - Sunitinib base of formula (I) and its pharmaceutically acceptable malate salt of formula (I(a)).
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Page/Page column 44
(2010/01/30)
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- POLYMORPHS OF SUNITINIB BASE AND PROCESSES FOR PREPARATION THEREOF
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The present invention provides polymorphs of Sunitinib base and processes for preparation thereof.
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Page/Page column 34-35
(2009/06/27)
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