- Method for utilizing microchannel reactor to synthesize paliperidone midbody
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The invention discloses a method for utilizing a microchannel reactor to synthesize a paliperidone midbody, and belongs to the technical field of psychotropic medicine synthesis in organic synthesis.By means of the method, a paliperidone hydrogen-adding reaction precursor 3-(2-chloroethyl)-2-methyl-9-hydroxyl-4H-pyridino-[1,2-A]pyrimidine-4-ketone is added into an organic solvent, after a catalyst of activated-carbon-loaded precious metal is added, the mixture is used as a first material, and the first material is delivered into a preheating module of the microchannel reactor to be preheated;the preheated first material and hydrogen are delivered to a reaction module of the microchannel reactor separately to be reacted, reaction liquid flowing out of an outlet of the microchannel reactoris collected, and the paliperidone midbody is obtained through aftertreatment. By means of the synthesis method, the reaction time can be effectively shortened, the potential safety hazard of a hydrogen leakage combustion explosion is greatly lowered, and the method is applicable to synthesizing the paliperidone midbody.
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Page/Page column 7-11
(2018/05/30)
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- Preparation method of high-purity paliperidone intermediate
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The invention belongs to the technical field of medicine, and particularly discloses a preparation method of a high-purity paliperidone intermediate 3-(2-chloroethyl)-9-hydroxyl-2-methyl-6,7,8,9-tetrahydro-4H-pyridino[1,2-a] pyrimidine-4-ketone. The preparation method particularly comprises the following steps: preparing 9-(benzyloxy)-3-(2-chloroethyl)-2-methyl-4H-pyridino[1,2-a] pyrimidine-4-ketone by taking 2-amino-3-hydroxypyridine as a starting raw material and through benzyl protection, ring closure of alpha-acetyl-gamma-butyrolactone and chloro-substitution; dissolving the 9-(benzyloxy)-3-(2-chloroethyl)-2-methyl-4H-pyridino[1,2-a] pyrimidine-4-ketone into an alcohol solvent, adding acid and a palladium-charcoal catalyst, controlling hydrogen pressure, and after the reaction is completed, performing processes of filtering, concentrating, adjusting the pH value, extracting, concentrating and refining to obtain white-like powdered 3-(2-chloroethyl)-9-hydroxyl-2-methyl-6,7,8,9-tetrahydro-4H-pyridino[1,2-a] pyrimidine-4-ketone. The preparation method is short in cycle, the product is white-like, the yield reaches 70 percent or higher, the purity reaches 99 percent or higher, related impurities of chlorine-removed byproducts are avoided, and the preparation method is suitable for industrialized enlarged production.
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- Processes for the preparation of paliperidone
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The present invention relates to a novel process for the preparation of paliperidone and its intermediates and also relates to an improved process for the preparation of paliperidone compound of formula (I).
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Paragraph 19
(2013/07/25)
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- PROCESS FOR PREPARATION OF PALIPERIDONE
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The present invention relates to an improved process for the preparation of pure Paliperidone of Formula I.
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Page/Page column 11
(2012/04/17)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PALIPERIDONE
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The present invention relates to a process for preparation and purification of 3-[2-[4-(6- fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H- pyrido[1,2-a]pyrimidin-4-one, also known as paliperidone or 9-hydroxy risperidone.
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- PROCESS FOR PREPARING PALIPERIDONE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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The present invention discloses the process for the preparation of paliperidone and its pharmaceutically acceptable salts comprising (a) condensing 2-amino-3-hydroxy- pyridine with 2-acetylbutyro lactone in the presence of an acid catalyst to isolate 9- hydroxy-3-(2-hydroxyethyl)-2-rnethyl-4H-pyrido[l, 2-a] pyrimidin-4-one; treating 9- hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[l, 2-a] pyrimidin-4-one with a chlorinating agent; hydrogenating the product in the presence of one or more lewis acids to obtain 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrrido[l,2-a]- pyrimidin-4-one; and condensing3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2- methyl-4H-pyrrido[l,2-a]-pyrimidin-4-one. The present invention also discloses processes for the preparation of intermediates useful in the preparation of paliperidone and its pharmaceutically acceptable salts.
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Page/Page column 15
(2011/07/07)
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- NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF PALIPERIDONE
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The present invention relates to a novel process for the preparation of paliperidone and its intermediates and also relates to an improved process for the preparation of paliperidone compound of formula (I).
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PURE PALIPERIDONE
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The present invention relates to an improved process for the preparation of pure Paliperidone of formula (I). The present invention more specifically provides an improved process for the preparation of pure Paliperidone which may contain impurities in the acceptable level of pharmacopoeia requirement specifically 3-{2-[4-(5-Fluoro-benzo[d]isoxazol-3-yl]-piperidin-1-yl]-ethyl}-2- methyl-7,8-dihydro-6H-pyrido[1,2-a]pyrimidine-4,9-dione of Formula (IV).
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Page/Page column 11
(2011/02/24)
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- SYNTHESIS OF PALIPERIDONE
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A compound of formula (6) or an acid addition salt thereof in which G is (i) a leaving group A selected from a halo group and a sulfonyloxy group, or (ii) a group of the formula (20) is useful in processes of making paliperidone and related compounds.
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Page/Page column 11
(2010/02/17)
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- PROCESS OF SYNTHESIS OF PALIPERIDONE
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The invention relates to an improved process for preparation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one, an intermediate used in the synthesis of paliperidone and process for converting the same to Paliperidone.
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Page/Page column 7
(2010/06/20)
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- NOVEL AND IMPROVED PROCESSES FOR THE PREPARATION OF PALIPERIDONE
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The present invention relates to a novel process for the preparation of paliperidone and its intermediates and also relates to an improved process for the preparation of paliperidone compound of formula (I).
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Page/Page column 10; 19
(2010/04/03)
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- NOVEL COMPOUNDS FOR TREATMENT OF PSYCHOTIC DISORDERS, PREPARATION METHODS AND USES THEREOF
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The present invention relates to a compound of formula (I), an optical isomer or a pharmaceutically acceptable salt thereof, its preparation and uses, wherein R is defined as herein. Such compounds can be presented as an optical isomer or a racemic mixture. The compounds can be metabolized in vivo to form a pharmacologically active substance as antagonist of neurotransmitters, and can be used for the treatment of the related mental disorders such as schizophrenia.
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Page/Page column 7
(2010/03/04)
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- PROCESS FOR THE PREPARATION OF PALIPERIDONE AND ITS INTERMEDIATES
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A process for the preparation of a psychotropic agent Paliperidone. Preferably, this invention relates to a method for the purification of Paliperidone by making its acid addition salts.
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Page/Page column 6
(2010/12/29)
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- Processes for the Preparation of Paliperidone and Pharmaceutically Acceptable Salts Thereof and Intermediates for Use in the Processes
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The present invention relates to novel compounds of formula (VIII) and (X), processes for their preparation and their use in the preparation of paliperidone or a salt thereof. There is also provided by the present invention novel processes for preparing intermediates for use in the preparation of paliperidone or a salt thereof, and novel processes for preparing paliperidone or a salt thereof.
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Page/Page column 14
(2010/12/29)
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- A PROCESS FOR THE PREPARATION OF PALIPERIDONE INTERMEDIATES
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The present invention relates to a process for the preparation of 3-(2-chloroethyl)-6, 7, 8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrrido[1,2-a]-pyrimidin-4-one; and its use in the synthesis of paliperidone.
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Page/Page column 17-18
(2009/12/05)
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- PROCESS TO PREPARE PALIPERIDONE AND INTERMEDIATES THEREOF
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The present invention relates to an improved process for obtaining Paliperidone, I, comprising alkylating compound VI, or a salt thereof, with compound V, or a salt thereof, using a base selected from triethylamine or diisopropylethylamine and, optionally, a solvent. Moreover, the invention relies on the preparation of intermediates used in such process.
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Page/Page column 13-14
(2009/12/27)
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- AN IMPROVED, INDUSTRIALLY VIABLE PROCESS FOR THE PREPARATION OF HIGH PURITY PALIPERIDONE
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The present invention relates to an improved and industrially viable process for the preparation of high purity ≥ 99.8% chemical of paliperidone of formula-I (3-[2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl]ethyl]-6,7,8,9-tetra-hydro-9-hydroxy-2- methyl-4H-pyrido[l,2-a]pyrimidin-4-one), involving the novel intermediate, 3-(2- hydroxyethyl)-2-methyl-9-(phenylmethoxy)-4H-Pyrido[l,2-a]pyrimidin-4-one of formula-II. All intermediates encountered in the synthetic pathway of present invention are isolated by simple crystallization techniques in high pure. Paliperidone is useful as anti-psychotic agent in the treatment of psychotic disorders and is marketed under the brand name INVEGA.
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Page/Page column 14-15
(2009/03/07)
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- Novel Intermediate for the Preparation of Paliperidone
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A new compound of formula (IV) R represents a protecting group which is removable by hydrogenation, and use thereof as an intermediate for preparing paliperidone.
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Page/Page column 3-4
(2009/07/25)
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- PREPARATION OF PALIPERIDONE
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Processes for preparing paliperidone.
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- AN IMPROVED PROCESS FOR PREPARATION OF PALIPERIDONE
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The present invention relates to a process for preparation and purification of 3-[2-[4- (6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl- 4H-pyrido[l,2-a]pyrimidin-4-one, also known as paliperidone or 9-hydroxy risperidone. The invention also relates to the preparation of intermediates useful in the process.
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Page/Page column 11-12
(2009/10/22)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PALIPERIDONE AND ITS INTERMEDIATES
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The present invention relates to a process for the preparation of a psychotropic agent Paliperidone. Preferably, this invention relates to a method for the purification of Paliperidone by making its acid addition salts.
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Page/Page column 14-15
(2009/06/27)
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- PROCESS FOR THE SYNTHESIS OF CMHTP, A PALIPERIDONE INTERMEDIATE
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The present invention provides a process for 3-(2-chloroethyl)-6,7,8,9- tetrahydro-9-hydroxy-2-methyl-4H-pyrrido[1,2-a]- pyrimidin-4-one (CMHTP), and its conversion to paliperidone.
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Page/Page column 6
(2009/05/29)
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- IMPROVED PROCESS FOR PREPARING PALIPERIDONE, NOVEL POLYMORPHIC FORMS OF THE SAME AND PROCESS THEREOF
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Disclosed herein is an improved process for producing paliperidone, wherein the process includes hydrogenating 3-(2-chloroethyl)-2-methyl-9-(hydroxyprotected)-4H- pyrido[1.2-a] pyrimidin-4-one in presence of an acid and a catalyst under hydrogen pressure to give 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H- pyrido[l,2-a]-pyrimidin-4-one and condensing 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9- hydroxy-2-methyl-4H-pyrido[l,2-a] -pyrimidin-4-one with 6-fluoro-3-(4-piperidinyl)- 1,2-benzisoxazole in presence of a base and a solvent to give paliperidone. In addition, the invention discloses novel polymorphic Forms VI and VII of paliperidone. Furthermore the invention discloses processes for producing the novel polymorphic forms and Form I from the novel polymorphic forms thereof.
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Page/Page column 6; 12
(2009/05/29)
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- 3-[2-[4-(6-FLUORO-1,2-BENZISOXOZOL-3-YL)-1-PIPERIDINYL]ETHYL]-6,7,8,9 TETRAHYDRO-9-HYDROXY-2-METHYL-4H-PYRIDO [1,2-A]PYRIMIDIN-4-ONE, COMPOSITIONS AND METHOD OF USE
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The present invention relates to novel 3-piperidinyl-1,2-benzisoxazoles having long-acting antipsychotic properties and which are useful in the treatment of warm-blooded animals suffering from psychotic diseases. Methods of preparing said compounds and compositions containing the same.
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