- MANUFACTURING METHOD OF DULOXETINE HYDROCHLORIDE AND DULOXETINE HYDROCHLORIDE WITH NOVEL CRYSTAL STRUCTURE
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PROBLEM TO BE SOLVED: To provide a method of providing crystal of (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (general name:duloxetine hydrochloride) useful as an antidepressant with high purity and high bulk density. SOLUTION: There is provided a manufacturing method of duloxetine hydrochloride for depositing the duloxetine hydrochloride in a resulting mixture by mixing a solution by dissolving duloxetine hydrochloride into a solvent for dissolution containing at least one kind of polar solvent selected from water and alcohol having 1 to 3 carbon atoms with acetone, and setting a temperature when dissolving the duloxetine hydrochloride into the solvent for dissolution at 60°C or less. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0027; 0053
(2018/10/10)
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- IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALT
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The present invention relates to an improved process for racemizing one of the enantiomers, or an enantiomerically enriched mixture, of an optically active compound (S)-N, N-dimethyl-3-(2-thienyl)-3-hydroxypropanamine, a key intermediate used for the preparation of (S)-N-methyl-3-(1-naphthalenyloxy)-3-(2- thienyl) propanamine (duloxetine) or its hydrochloride salt. Moreover, the present invention also relates to an improved process for the preparation of (S)-N-methyl-3- (1-naphthalenyloxy)-3-(2-thienyl) propanamine (duloxetine) or its hydrochloride salt having low content of undesired R-isomer and chiral purity not less than 99%.
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- METHOD FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
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The present invention relates to an improved process for the preparation of Duloxetine and its intermediates (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine by reacting (S)-(+)-N,N-dimethyl-3-(2-thienyl)-3-hydroxypropanamine with 1-fluoronaphthalene in the presence of a base; wherein the improvement lies in conducting the reaction in the absence of solvent.
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Page/Page column 3
(2010/11/03)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE AND SALTS THEREOF
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The present invention relates to improved process for the preparation of Duloxetine of formula (I) and salts thereof wherein said improvement takes place in step of condensation.
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Page/Page column 7-8
(2010/08/04)
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- Gastro-resistant pharmaceutical oral compositions comprising duloxetine or its pharmaceutically acceptable derivatives
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The present invention relates to a pharmaceutical composition comprising an active core comprising duloxetine or its pharmaceutically acceptable derivatives, a separating layer comprising a water soluble alkaline substance and a gastro-resistant coating comprising a gastro-resistant polymer selected from methacrylic acid copolymers and optionally an over-coating layer.
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- An investigation on key parameters that influence the synthesis of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propylamine: A key intermediate for duloxetine
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This document highlights the systematic study of influencing factors such as temperature, base, catalyst, and solvent volume in the synthesis of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propylamine oxalate 11a, without affecting the chiral
- Suthrapu, Sashikanth,Sripathi, Somaiah,Veeramalla, Raju,Bojja, Ramachandra Reddy,Karnati, Venugopal Reddy
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experimental part
p. 854 - 856
(2010/04/22)
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- A METHOD FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
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The present invention relates to an improved process for the preparation of Duloxetine and its intermediates (S)-(+)-N,N-dimethyl-3-(l-naphthalenyloxy)-3-(2- thienyl)propanamine by reacting (S)-(-)-N,N-dimethyl-3-(2-thienyl)-3-. hydroxypropanamine with 1-fluoronaphthalene in the presence of a base; wherein the improvement lies in conducting the reaction in the absence of solvent.
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Page/Page column 7-8
(2009/09/04)
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- SYNTHESIS AND PREPARATIONS OF DULOXETINE SALTS
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The invention relates to an improved process for the preparation of duloxetine hydrochloride.
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Page/Page column 6
(2009/04/24)
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- NOVEL PROCESS FOR PREPARATION OF DULOXETINE HYDROCHLORIDE
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An improved, safer and easy to operate on plant scale process for synthesis of duloxetine hydrochloride (1) having chiral purity greater than 99.9% that is characterized by the following: (i) preparation of racemic condensed compound (RS)-N,N-di methyl-3- (1-naphthyloxy)-3-(2-thienyl)propanamine (4) by reaction of racemic hydroxy compound (2) with 1-fluronaphthalene (3) in presence of a base such as sodamide, potassium amide or potassium bis(trimethylsilyl)amide (KHDMS) in polar aprotic solvent, (ii) optical resolution of racemic condensed compound (5a + 5b) with di-benzoyl-L-tartaric acid (7, DBTA, R = H) or di-para-anisoyl-L-tartaric acid (7, DATA, R = OCH3) to obtain crude (S)-N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine dibenzoyl tartarate salt (8a) or (S)-N.N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine di-p-anisoyl tartarate salt (9a) respectively, (iii) optionally purification of crude tartarate salts (8a or 9a) by crystallization, (iv) optionally purification of duloxetine hydrochloride (1) by crystallization and (v) racemization of undesired (R)-N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (5b) by treatment with base potassium bis(trimethylsilyl)amide (KHDMS) to obtain racemic mixture of condensed compounds (5a and 5b). A novel salt S(+)-N.N-dimethyl-3-(1-naphthylenyloxy)-3-(2-thienyl)propanamine dibenzoyl -(L)- tartarate (8a) and S(+)-N.N-dimethyl-3-(1-naphthylenyloxy)-3-(2-thienyl)propanamine di-p-anisoyl-(L)- tartarate (9a). Novel process for racemization of undesired (R)-N,N-di methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine (5b) by treatment with KHDMS to obtain racemic mixture condensed compounds (5a and 5b).
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Page/Page column 20; 21
(2008/12/07)
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- Process for the Preparation of 1-Naphthol Mixed Ethers and Intermediates of Crystalline Forms of (+) and (-)-Duloxetine
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The invention relates to a process for the preparation of duloxetine (1a), comprising the reaction between 1-fluoronaphthalene and 3-N,N-dimethylamino-1-(2-thienyl)-propan-1-ol in the presence of 1,3-dimethyl-2-oxo-hexahydropyrimidine (DMPU) as the solvent; a method for the identification of duloxetine enantiomers and for the determination of its optical purity is also disclosed.
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Page/Page column 2
(2008/12/09)
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- DNT-MALEATE AND METHODS OF PREPARATION THEREOF
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(S)-N,N-Dimethyl-3-(l-naphtlialenyloxy)-3-(2-thienyl)propanamine nialeate (DNT-maleate) and polymorphs of DNT-maleate, compositions of DNT-maleate and its polymorphs, processes for the preparation of DNT-maleate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-maleate are provided.
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Page/Page column 19
(2010/11/26)
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- PROCESS FOR THE PREPARATION OF DULOXETINE
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The invention relates to a process for the preparation of duloxetine (1a), comprising the reaction between 1-fluoronaphthalene and 3-N,N-dimethylamino-l-(2-thienyl)-propan-l-ol in the presence of l,3-dimethyl-2-oxo-hexahydropyrimidine (DMPU) as the solvent; a method for the identification of duloxetine enantiomers and for the determination of its optical purity is also disclosed.
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Page/Page column 5-7
(2008/06/13)
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- A process for the preparation of an intermediate useful for the asymmetric synthesis of (+)duloxetine
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A process for the preparation of (+)duloxetine, or an acid addition salt thereof, comprising: (i) Resolving racemic (±)N-methyl duloxetine with a less than stoichiometric amount of a chiral acid in combination with suitable amounts of a hydrohalogen acid to give a salt of the chiral acid and (+)N-methyl duloxetine, substantially free from (-)N-methyl duloxetine; (ii) Demethylating the (+)N-methyl duloxetine prepared in step (i) to give (+)duloxetine or another acid addition salt in enantiomerically pure form.
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Page/Page column 5
(2010/11/28)
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- DNT-FUMARATE AND METHODS OF PREPARATION THEREOF
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(S)-N,N-Dimethyl-3-(l-naphthalenyloxy)-3-(2-thienyl)propanamine fumarate (DNT-fumarate) and polymorphs of DNT-fumarate, compositions of DNT-fumarate and its polymorphs, processes for the preparation of DNT-fumarate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-fumarate are provided.
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Page/Page column 15
(2008/06/13)
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- DNT-succinate and methods of preparation thereof
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(S)-N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine succinate (DNT-succinate) and polymorphs of DNT-succinate, compositions of DNT-succinate and its polymorphs, processes for the preparation of DNT-succinate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-succinate are provided.
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Page/Page column 6
(2010/11/28)
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- A PROCESS FOR PREPARATION OF AN ANTIDEPRESSANT COMPOUND
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The present invention provides optically pure (S)-(+)-N-methyl-3-(1-naphthaleneoxy)-3-(2-thienyl)propanamine, a compound of formula (I), and optically pure (S)-isomer of compound of formula 4, wherein R1 and R2 both are methyl or R1 is methyl and R2 is benzyl or substituted benzyl group and process for preparation thereof. Formula (I) and (IV). In another aspect the present invention provides a process for preparation of an acid addition salt of compound of formula (I).
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Page/Page column 21; 22
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE
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A process for preparing Duloxetine, or its acid addition salt, which process comprises (i) condensation of (S)-(-)-N, N-dimethyl-3-(2-thienyl)-3-hydroxy propanamine with 1-fluoronaphthalene followed by demethylation or condensation of N, N-dimethyl-3-(2-thienyl)-3-hydroxy propanamine with 1-fluoronaphthalene followed by resolution and demethylation; and (ii) if desired, converting Duloxetine to its acid addition salt.
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Page/Page column 5; 7-8
(2010/11/25)
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- A PROCESS FOR PREPARING DULOXETINE AND INTERMEDIATES FOR USE THEREIN
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A process for preparing (+)duloxetine, or an acid addition salt thereof, which process comprises resolving racemic (±)duloxetine with a chiral acid so as to obtain a salt of the chiral acid and (+)duloxetine, substantially free of (-)duloxetine; and (ii) if desired, converting the salt prepared in step (i) to the free base or another acid addition salt as appropriate. The process for preparing (+)duloxetine, or an acid addition salt thereof, can further comprise an O-alkylation intermediate process step which is carried out in the presence of a base and a phase transfer catalyst.
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- Chiral synthesis of 1-aryl-3-aminopropan-1-ols
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This invention is directed to a process for preparing chiral 1-aryl-3-amino-propan-1-ols. These compounds are important intermediates in the synthesis of pharmacologically active compounds.
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- ASYMMETRIC SYNTHESIS AND ABSOLUTE STEREOCHEMISTRY OF LY248686
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Reduction of 3-(dialkylamino)-1-aryl-1-propanones with a 2 : 1 complex of (8) and lithium aluminum hydride (LAH) provided the corresponding 1,3-diaminoalcohols in high ee's (80-88percent).This process was developed and applied to the synthesis of LY248686 (1), a potent inhibitor of serotonin (5HT) and norepinephrine (NE) uptake.Absolute configurations have been established by single crystal x-ray analysis.
- Deeter, Jack,Frazier, Jeff,Staten, Gilbert,Staszak, Mike,Weigel, Leland
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p. 7101 - 7104
(2007/10/02)
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- 3-aryloxy-3-substituted propanamines
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The present invention provides 3-aryloxy-3-substituted propanamines capable of inhibiting the uptake of serotonin and norepinephrine.
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