- For the preparation of asenapine and used for preparing intermediates of asenapine
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The invention relates to a method for preparing asenapine shown in a general formula (9) and an intermediate shown in a general formula (7) and used for preparing asenapine. The general formulas are shown in the specification. The method comprises the step that asenapine shown in the general formula (9) is obtained through ring-closure reaction of a compound shown in a general formula (8).
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- For the preparation of asenapine and used for preparing intermediates of asenapine
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The invention relates to a method for preparing asenapine shown in a general formula (11) and an intermediate shown in a general formula (8) and used for preparing asenapine. The general formulas are shown in the specification. The method comprises the following steps: obtaining a compound shown in a general formula (9) through ring-closure reaction of the compound shown in the general formula (8); obtaining a compound shown in a general formula (10) through reduction reaction of the compound shown in the general formula (9); obtaining asenapine shown in the general formula (11) through substitution reaction of the compound shown in the general formula (10), wherein in the general formula (8), R1 represents halogen, preferably chlorine or bromine.
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Paragraph 0211; 0253-0257
(2019/01/22)
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- A process for the preparation of key intermediate asenapine
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The invention provides a chemical synthesis method, in particular to a preparation method of a key intermediate [formula (III)] compound of asenapine capable of serving as a schizophrenia drug. In an anhydrous system, the intermediate [formula (III)] compound is obtained through dehydration of an intermediate [formula (II)] compound and anhydride under the action of a catalyst. The invention further provides a novel method for preparing asenapine by the intermediate [formula (III)]. The provided method has the advantages of simple operation, high yield, environment-friendliness, lower cost, stable technology and the like.
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- PROCESS FOR THE PREPARATION OF ASENAPINE MALEATE
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The present invention provides a process for the preparation of asenapine maleate of Formula (I), comprising: intra-molecular cyclization of the intermediate of Formula (II) to obtain the intermediate of Formula (III) using aluminium halide.
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- PROCESS FOR THE PREPARATION OF ASENAPINE INTERMEDIATE
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The present invention provides a process for the preparation of the asenapine intermediate of Formula (III) using a magnesium-methanol-acetic acid mixture.
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Paragraph 0034
(2014/11/27)
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- COMPRESSED ORAL DOSAGE FORM FOR ASENAPINE MALEATE
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The present invention relates to a compressed pharmaceutical dosage form intended for sublingual or buccal administration and capable of being rapidly disintegrated, the compressed pharmaceutical dosage form containing asenapine maleate in a microcrystalline monoclinic form. It further relates to a method of preparing the same and to a container comprising the dosage form.
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Page/Page column 28
(2013/04/10)
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- A PROCESS FOR THE PREPARATION OF ASENAPINE AND NOVEL SALTS THEREOF
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A process for preparation of asenapine of formula (1) or its acid addition salts; The said process comprises preparation of trans racemate of asenapine by reacting trans- 1 1-chloro-2,3,3a, 12b-tetrahydro-2-methyl-lH-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-l-one with mixture of aluminium chloride and lithium aluminium hydride in solvent followed by converting it into acid addition salt of asenapine followed by hydrolyzing the acid addition salt into trans racemate asenapine base and converting the asenapine base into acid addition salt. Asenapine sulphate of formula (Via) and asenapine maleate of formula (IVb) are also disclosed. The co-precipitate of acid addition salt of asenapine with a pharmaceutically acceptable excipient of formula (V); is also disclosed.
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Page/Page column 24
(2013/03/26)
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- PROCESS FOR THE PREPARATION OF ASENAPINE INTERMEDIATE
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The present invention provides a process for the preparation of the asenapine intermediate of Formula (III) using a magnesium-methanol-acetic acid mixture.
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Page/Page column 9; 10
(2013/06/27)
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- PROCESS FOR THE PREPARATION OF (3ARS,12BRS)-5-CHLORO-2-METHYL-2,3,3A12B-TETRAHYDRO-1HDIBENZO[2,3:6,7] OXEPINO [4,5-C]PYRROLE MALEATE AND IT'S PHARMACEUTICAL COMPOSITION THEREOF
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The present invention relates to an improved process for the preparation (3aRS,12bRS)-5-Chloro-2-menthyl-2,3,3a,12b-tetrahydro-1Hdibenzo[2,3:6,7]oxepino [4,5-c]pyrrole maleate represented by the compound of formula-1a and its pharmaceutical composition.(F)
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- NOVEL PROCESS FOR THE PREPARATION OF ASENAPINE
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The present invention is directed to novel compounds of formula (I) as well as to the process for their preparation. Novel compounds of formula (I) can be converted into asenapine through an efficient process. The invention also relates to novel intermediates used in this process and their use in the preparation of compounds of formula (I).
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- CRYSTALLINE SALTS OF ASENAPINE
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Disclosed is asenapine phosphate of formula (I) and its enantiomer (I) which can be used to prepare asenapine maleate. Further disclosed is a monoclinic crystalline form of asenapine maleate.
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Page/Page column 11-12
(2012/11/14)
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- Novel Crystalline Asenapine Hydrochloride Salt Forms
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The invention relates to novel crystalline HCl salts of Asenapine and to methods of their preparation. Furthermore the invention relates to the use of the novel salts in pharmaceutical compositions and the use of the novel salts in the treatment of psychotic diseases or disorders such as schizophrenia and acute mania associated with bipolar disorder.
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Page/Page column 9
(2012/12/13)
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- Novel crystalline salts of Asenapine with organic Di-acids and Tri-acids
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The invention relates to novel crystalline salts of Asenapine with organic di-acids and tri-acids and to methods of their preparation. Furthermore the invention relates to the use of the novel salts in pharmaceutical compositions and to the use of the novel salts as medicaments, preferably in the treatment of psychotic diseases or disorders such as schizophrenia and acute mania associated with bipolar disorder.
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Page/Page column 9
(2012/12/13)
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- Novel Crystalline Salts of Asenapine
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The present invention relates to novel crystalline salts of Asenapine and to methods of their preparation. In particular, the invention relates to crystalline Asenapine salts of tartaric acid or succinic acid, wherein the salts are e.g. selected from the group consisting of Asenapine D, L-tartrate hydrate form A, Asenapine D, L-tartrate hydrate form B, Asenapine D, L-tartrate anhydrous form , Asenapine succinate form X, Asenapine succinate form , and Asenapine succinate form II. Furthermore the present invention relates to pharmaceutical compositions comprising the novel salts and to the novel salts for use in the treatment of psychotic diseases or disorders.
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Page/Page column 9-10
(2012/12/13)
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- NEW CRYSTAL FORMS OF THE SALT OF TRANS-5-CHLORO-2-METHYL-2,3,3A,12b-TETRAHYDRO-1H-DIBENZO[2,3:6,7]OXEPINO[4,5-c]PYRROLE WITH MALEIC ACID
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The present invention relates to two new crystal forms of the salt of trans-5-chloro-2- methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrolewith maleic acid, processes for preparing thereof and compositions comprising thereof. These new crystal forms of the salt of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenzo[2,3:6,7]oxepino[4,5-c]pyrrolewith maleic acid are stable under micronization and show an improved water solubility when compared to other asenapine maleate crystalline forms described in the prior art, such as the orthorhombic form (form L) and the monoclinic form (form H).
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Page/Page column 33-34
(2012/10/07)
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- PROCESS FOR THE PREPARATION OF TETRACYCLIC DERIVATIVES AND INTERMEDIATE PRODUCTS USED IN THE PROCESS
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A process for preparation of a compound of formula I or a pharmaceutically acceptable salt thereof, is disclosed. The process involves subjecting a compound of formula II to Ullmann-type conditions to effect an intra-molecular ring closure reaction to form the compound of formula I. The different substituents are as described in the specification. Further, the process can provide an alternate route for the synthesis of asenapine from starting materials that can be readily available.
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- ASENAPINE MALEATE
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Aspects of the present application relate to a microcrystalline monoclinic form of asenapine maleate represented by structural Formula (I); processes for its preparation; and pharmaceutically acceptable dosage forms thereof.
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- Intermediate compounds for the preparation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole
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Disclosed are novel amino acid derivatives of formula (I) and (II) processes for the preparation thereof, and their use in the preparation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrole.
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Page/Page column 9
(2010/11/24)
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- The syntheses of radiolabelled Org 5222 and its main metabolites Org 30526
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The syntheses of trans-5-chloro-2,3,3a-12b-tetrahydro-2-methyl-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrole (Org 5222), a potential antipsychotic compound, labelled with 3H, 14C and 36C1 and trans-5-chloro-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]-oxepino[4,5-c] pyrrole (Org 30526) labelled with 3H are described. 3H-labelled Org 5222 of low specific activity was prepared by a base catalyzed exchange with tritiated water of an amide precursor, 3H-labelled Org 5222 with a high specific activity by a catalytic reductive dehalogenation. 3H-labelled Org 30526 was prepared both by demethylation of 3H-Org 5222 and by catalytic reductive iodination of 11-iodo-Org 30526. 14C-labelled Org 5222 was synthesized in 6 steps using 14C-sarcosine as starting material. 36C1-labelled Org 5222 was prepared by diazotation reaction in the presence of H36C1.
- Vader,Kaspersen,Sperling,Schlachter,Terpstra,Hilberink,Wagenaars
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p. 845 - 869
(2007/10/02)
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- Biotransformation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate in rats
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The metabolism of trans-5-chloro-2-methyl-2,3,3a-12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222) labelled with [3H] or [14C] was investigated in Wistar rats. Metabolites were identified by mass spectrometry, 13C- and 1H-NMR analysis, IR spectroscopy and, wherever possible, by comparison with authentic reference compounds. The metabolites found in plasma, bile, faeces and urine revealed the processes of metabolism in which Org 5222 underwent oxidation to yield an N-oxide existing in two diastereoisomeric forms, or N-demethylation to yield a demethyl metabolite. A novel metabolite was found in bile viz. a carbamate glucuronide, formed from an intermediate carbamic acid, derived from the addition of CO2 to the demethyl metabolite.
- d. Wildenberg,Delbressine,Kaspersen,Wagenaars,Jacobs
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p. 540 - 544
(2007/10/02)
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