- Preparation method of risperidone
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The invention discloses a preparation method of risperidone, and belongs to the technical field of preparation methods for chemical medical intermediates. High-purity risperidone is prepared by performing oximation, cyclization and condensation reactions on 2,4- difluorophenyl-4,-piperidone methanone hydrochloride and 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyridino-[1,2-a]pyridine-4-ketone as raw materials. The method disclosed by the invention has the advantages of adoption of relatively cheap and readily-available raw materials, easiness in operation, higher yield and higher industrial value.
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- Spectroscopic and thermal investigations on the charge transfer interaction between risperidone as a schizophrenia drug with some traditional π-acceptors: Part 2
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The focus of present investigation was to assess the utility of non-expensive techniques in the evaluation of risperidone (Ris) in solid and solution states with different traditional π-acceptors and subsequent incorporation of the analytical determination into pharmaceutical formulation for a faster release of risperidone. Charge-transfer complexes (CTC) of risperidone with picric acid (PA), 2,3-dichloro-5,6-dicyano-p-benzoquinon (DDQ), tetracyanoquinodimethane (TCNQ), tetracyano ethylene (TCNE), tetrabromo-p-quinon (BL) and tetrachloro-p-quinon (CL) have been studied spectrophotometrically in absolute methanol at room temperature. The stoichiometries of the complexes were found to be 1:1 ratio by the photometric molar ratio between risperidone and the π-acceptors. The equilibrium constants, molar extinction coefficient (εCT) and spectroscopic-physical parameters (standard free energy (ΔGo), oscillator strength (f), transition dipole moment (μ), resonance energy (RN) and ionization potential (ID)) of the complexes were determined upon the modified Benesi-Hildebrand equation. Risperidone in pure form was applied in this study. The results indicate that the formation constants for the complexes depend on the nature of electron acceptors and donor, and also the spectral studies of the complexes were determined by (infrared, Raman, and 1H NMR) spectra and X-ray powder diffraction (XRD). The most stable mono-protonated form of Ris is characterized by the formation of +NH (pyrimidine ring) intramolecular hydrogen bonded. In the high-wavenumber spectral region ～3400 cm-1, the bands of the +NH stretching vibrations and of the pyrimidine nitrogen atom could be potentially useful to discriminate the investigated forms of Ris. The infrared spectra of both Ris complexes are confirming the participation of +NH pyrimidine ring in the donor-acceptor interaction.
- El-Habeeb, Abeer A.,Al-Saif, Foziah A.,Refat, Moamen S.
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p. 464 - 477
(2013/04/23)
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- PROCESS FOR PREPARATION OF RISPERIDONE
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The invention provides a more handy and environment friendly process for preparing risperidone, which comprises reacting 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride with 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one in a basic aqueous solution or suspension. The concentration of alkaline metal carbonates in the basic aqueous solution or suspension is ranged from 15% to 40%. The reaction is carried out at a temperature range of 101-140° C. and the reaction is completed within 10 minutes to 2 hours.
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Page/Page column 4
(2010/06/14)
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- PROCESS FOR PREPARING RISPERIDONE
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The present invention concerns an improved process of preparing risperidone (I).
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Page/Page column 5
(2009/07/18)
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- A PROCESS FOR THE PREPARATION OF RISPERIDONE
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The present invention relates to an improved process for the preparation of Risperidone of formula (I) by condensing 6-fluoro-3- (4-piperidinyl)-l, 2- benzisoxazole with 3-(2-chloroethyl)-6, 7, 8, 9-tetrahydro-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-one in water and water immiscible solvents under basic conditions in the presence of a catalyst. This invention also relates to a method for purification of crude Risperidone by removing an impurity specifically named as 9-hydroxy Risperidone to undetectable level using acid chlorides and an organic base in a suitable solvent.
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Page/Page column 7-9
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF RISPERIDONE
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The invention relates to a process for the preparation of risperidone (chemical name: 3-[2-[4-(6-fluoro-l,2-benzisoxazole-3-yl)-1piperidmyl]ethyl-2-methyl-6,7,8,9-terahydro-4H--pyrido[l,2-a]pyrimidine-4-one) of the formula (I) by reacting 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidine-4-one of the formula (II) and 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole of the formula (III), in which the reaction is carried out in dry methanol solvent under pressure, at a temperature between 65 and 90 °C, the product is recovered by using a methanol/water mixture of specified ratio and if desired is recrystallized from an alcohol.
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Page/Page column 6-7
(2008/06/13)
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- Process for the preparation of pure 3-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido [1,2-a] pyrimidin-4-one
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A process for the preparation of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one, which is known as Risperidone of Formula (I). Risperidone of Formula (I) is represented by the following structure.
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Page/Page column 2
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF RISPERIDONE
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The object of the invention is a process for the preparation of risperidone (chemical name: 3-[2-[4-(6-fluoro-l,2-benzisoxazole-3-yl)-l-piperidinyl]ethyl-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidine-4-one) of the formula (I) by reacting 6-fluoro-3-(4-piperidinyl)- 1,2-benzisoxazole of the formula (II), and 3-(2-iodoethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidine-4-one of the formula (III).
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Page/Page column 10
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF RISPERIDONE
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A process is provided for the preparation of risperidone of Formula (1); which process comprises reacting, in a condensation reaction, 6-fluoro-3-(4- piperidinyl)-1,2-benzisoxazole monohydrochloride of Formula (2) with 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2,a]pyrimidin-4-one monohydrochloride of Formula (3).
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Page/Page column 10-11
(2008/06/13)
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- Process for making risperidone and intermediates therefor
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The formation of risperidone is enhanced by the use of enriched Z-isomer oxime intermediate(s) of formula (3) or (7). The oxime(s) can be isomerically enriched by a variety of techniques including the use of the novel acetic acid salt thereof, which affords, inter alia, resolution of the isomers and/or by heat conversion.
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Page/Page column 8
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF ANTIPSYCHOTIC RISPERIDONE
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This invention relates to a process for the preparation of antipsychotic risperidone (Formula I); which comprises reacting 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one (Formula II); with 4-(2,4-difluorobenzoyl)piperidine oxime (Formula III); to form oxime (Formula IV); and in situ cyclization of oxime (Formula IV) to form risperidone (Formula I) in a solvent selected from the group consisting of acetonitrile, N,N-dimetylformamide and methyl isobutyl ketone.
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- IMPROVED PROCESS FOR PREPARATION OF RISPERIDONE
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The invention is for an improved process for of production of risperidone of formula (I) which comprises the steps of : (a) reacting a halo compound with an oxime ín a solvent and a base at 10-40°C; (b) refluxing the reaction mixture of step (a) for 4- 10 hours; (c) adding base to the cooled refluxed mixture of step (b) whileto maintaining the temperature at 20-40°C for 10-18 hours; (d) filtering and drying the risperidone thus obtained and (e) optionally purifying risperidone obtained in step (d). The invention also discloses a new polymorphic variety of risperidone namely, risperidone form T1 having its characteristic X-ray diffraction pattern and IR data.
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- METHOD FOR PREPARING RISPERIDONE
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Risperidone is prepared in a high yield by reacting 2,4-difluorophenyl(4-piperidinyl)methanone oxime hydrochloride and 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one in an aqueous alkali hydroxide solution having an alkali hydroxide concentration in the range of 20 to 40%.
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- PROCESS FOR PREPARING 3-(2-(4-(6-FLUOROBENZO(D) ISOXAZOL-3-YL)-PIPERIDIN-1YL)-ETHYL)-2-METHYL-6,7,8,9-TETRAHYDRO-4H-PYRIDO-(1,2-A) PYRIMIDIN-4-ONE
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The process consists in condensing (2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a] pyrimidin-3-yl)-acetaldehyde with 6-fluoro-3-piperidinyl)-1,2-benzisoxazole to yield the intermediate enamine, 3-[2-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]vinyl}-2-methyl--6,7,8,9-tetrahydro-pyrido [1,2,-a] pyrimidin-4-one followed by reduction of such an enamine.
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Page/Page column 12-13
(2008/06/13)
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- Preparation of risperidone
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The present invention is directed to the novel forms of risperidone, designated Form A, Form B and Form E. Methods for their preparation are also disclosed. The present invention also relates to processes for making risperidone. Pharmaceutical compositions containing the new forms of risperidone and methods of using them are also disclosed.
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- Combination treatment for anxiety, depression, obsessive compulsive disorder and psychosis
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The present invention relates to a method of treating depression, obsessive compulsive disorder and psychosis in a mammal, including a human, by administering to the mammal an atypical antipsychotic in combination with an antidepressant agent with improvement in efficiency. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, an atypical antipsychotic, and an SRI.
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- Method of inhibiting neurotransmitter activity using microencapsulated 3-piperidiny2-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
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A pharmaceutical composition comprising a biodegradable and biocompatible composition comprising a 1,2 benzazole within a polymeric matrix. The 1,2 benzazole composition, pharmaceutically acceptable acid addition salts thereof, are potent antagonists of a series of neurotransmitters, particularly serotonin and dopamine. A method of inhibiting both serotonergic overactivity and dopaminergic overstimulation in animals is provided by administration of a biodegradable and biocompatible microparticle composition comprising a 1,2 benzazole or a pharmaceutically acceptable acid addition salt thereof. A method of treating warm blooded animals suffering from psychotic disorders, and a method of preparing the biodegradable and biocompatible composition are also described.
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- 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
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3-Piperdinyl-1,2-benzisothiazoles and 3-piperidinyl-1,2-benzisoxazoles and their pharmaceutically acceptable acid addition salts having useful antipsychotic properties and being useful in the treatment of a variety of complaints in which serotonin release is of predominant importance.
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