- A new synthesis of oxcarbazepine using a Friedel-Crafts cyclization strategy
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A novel, simple, and straightforward process for the large-scale synthesis of oxcarbazepine, the active ingredient of Trileptal, a medicine for the treatment of epilepsy, has been developed. Starting from readily available 1,3-dihydro-1-phenyl-2H-indol-2-one, a Friedel-Crafts cyclization strategy provides a direct route to the tricyclic framework of the target molecule. Crucial to the success of the strategy was the choice of the proper nitrogen-protecting group.
- Kaufmann, Daniel,Fünfschilling, Peter C.,Beutler, Ulrich,Hoehn, Pascale,Lohse, Olivier,Zaugg, Werner
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- A new industrial process for oxcarbazepine
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A novel industrial process for the antiepileptic drug oxcarbazepine 1 has been developed. Unlike the old process, the new process is free from halogenated solvents and can be performed in standard production equipment. It starts from commercially available 1,3-dihydro-1-phenyl-2H-indol-2-one 10. In the key step, an electrophilic ring closure reaction of 2-[(methoxycarbonyl)phenylamino] benzeneacetic acid 5 to 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxylic acid methyl ester 6 in poly phosphoric acid was applied. For the manufacture of 5, a highly efficient process using a dianion strategy was developed.
- Fuenfschilling, Peter C.,Zaugg, Werner,Beutler, Ulrich,Kaufmann, Daniel,Lohse, Olivier,Mutz, Jean-Paul,Onken, Ulrich,Reber, Jean-Louis,Shenton, David
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- Synthesis method of high-purity stable crystal form of escilitalopine acetate
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The present invention discloses a high-purity method for the synthesis of escitazepine acetate and a novel stable crystal form thereof. The preparation method disclosed in the present invention is achieved by the following steps: 10-methoxyiminopyrene as the starting material, the starting material is dissolved in acetone and deprotected to form 10-carbonyliminocarbenzene; the use of dichloromethane, borane dimethyl sulfide, (R)-2-methyl -CBS- oxazoleboran asymmetrical reduction to generate (10S)-10-hydroxyiminopyrene; (10S)-10-hydroxyiminostilbeneylated into esters, amidated with chlorosulfonyl isocyanate, To obtain escilitalopine acetate and a stable new crystal form. The preparation method provided by the present invention is simple synthesis process, few reaction steps, less pollution, raw materials are readily available and inexpensive, the final product is easy to purify and separate and the crystal form is stable, and the industrial application prospects are broad.
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Paragraph 0029
(2022/03/18)
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- Iridium/f-Amphol-catalyzed Efficient Asymmetric Hydrogenation of Benzo-fused Cyclic Ketones
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Iridium/f-Amphol-catalyzed asymmetric hydrogenation of various benzo-fused five to seven-membered cyclic ketones was successfully developed, affording a series of chiral benzo-fused cyclic alcohols with excellent results (75%–99% yields, 93%–>99% ee, and TON up to 297 000). The enantioenriched products can be employed as key intermediates or motifs for the synthesis of some important biologically active compounds, such as rasagiline mesylate TVP-1012 used for the treatment of Parkinson's disease, the enantiomer of anticonvulsant drug eslicarbazepine acetate (BIA 2-093). (Figure presented.).
- Yin, Congcong,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 4319 - 4324
(2018/10/15)
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- ORGANIC COMPOUND AND ORGANIC ELECTROLUMINESCENT DEVICE COMPRISING THE SAME
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The present invention relates to a novel compound represented by chemical formula 1, and an organic electroluminescent device comprising the same. The compound according to the present invention can improve light-emitting efficiency, driving voltage, and lifespan of the organic electroluminescent device by being used in an organic layer of the organic electroluminescent device.COPYRIGHT KIPO 2016
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Paragraph 0136 - 0139
(2016/10/09)
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- ORGANIC COMPOUND AND ORGANIC ELECTROLUMINESCENT DEVICE COMPRISING THE SAME
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The present invention relates to a novel compound and an organic electroluminescent device comprising the same. The compound in accordance with the present invention is used in an organic material layer of the organic electroluminescent device, and thereby luminous efficiency, driving voltage, durability and other characteristics of an organic electroluminescent device can be improved.COPYRIGHT KIPO 2015
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Paragraph 0136-0139
(2016/10/08)
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- Application of nanoparticle mediated N-arylation of amines for the synthesis of pharmaceutical entities using vit-E analogues as amphiphiles in water
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The first CuI-nanoparticle catalyzed inter and intramolecular N-arylation of amines using vitamin E analogues (TPGS) as amphipiles has been developed in water. Application of this transition metal-amphiphile C-N bond formation methodology is further extended for the synthesis of substituted indoles, bioactive natural product tryptanthrin and intermediates of pharmaceutical entities such as imatinib, nilotinib, selective D3 agonist/antagonist ligands, and oxacarbazepine. This journal is
- Kumar, Atul,Bishnoi, Ajay Kumar
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p. 20516 - 20520
(2015/03/30)
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- Friedel-crafts chemistry. Part 39. unprecedented facile route to the synthesis of benzo[b][1]benzazepines via intramolecular friedel-crafts cyclialkylations
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A series of six pharmaceutically promising 5,6-dihydro-11H-benzo[b][1] benzazepine derivatives (1c-h) were cleanly prepared by Friedel-Crafts cyclialkylations of nitrogen-containing alkanols in the presence of AlCl3, 85% H2SO4 or polyphosphoric acid catalysts. The precursor alkanols (13a-f) were readily prepared by reaction of two synthesized carboxylic acid esters (12a, b) with different Grignard reagents. Also, two dibenzo[b,f]azepinones (15a, b) were prepared by Friedel-Crafts cycliacylation and reduced to the corresponding 5,6-dihydro-11H-benzo[b][1]benzazepines (1a, b). Overall, this approach allows easy and efficient access to polytricyclic amines from easily synthesized alkanols or cycloketones. A plausible carbocation mechanism is proposed to account for the results.
- El-Aal, Hassan A. K. Abd,Khalaf, Ali A.
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p. 635 - 645
(2013/07/26)
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- Mild and efficient synthesis of benzo-fused seven- and eight-membered ring lactams: A convenient approach to biologically interesting chemotypes
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A general and efficient method for the synthesis of benzo-fused 7- and 8-membered ring lactams via the Beckmann rearrangement of cyclic oximes is presented. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Kenwright, Jayne L.,Galloway, Warren R. J. D.,Wortmann, Lars,Spring, David R.
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supporting information
p. 1508 - 1516
(2013/05/21)
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- An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine
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Efficient methods have been developed for the synthesis of three active pharmaceutical ingredients (APIs) carbamazepine (Tegretol) 1, oxcarbazepine (Trileptal) 2, and eslicarbazepine acetate (Exalief) 3 by employing enantioselective reduction and carboxamidation reaction.
- Ravinder,Rajeshwar Reddy,Sridhar,Murali Mohan,Srinivas, Katkam,Panasa Reddy,Bandichhor, Rakeshwar
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supporting information
p. 2841 - 2844
(2013/06/26)
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- Corey-itsuno reduction of ketones: A development of safe and inexpensive process for synthesis of some API intermediates
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A safe and inexpensive procedure for asymmetric reduction of ketones using in situ prepared N,N-diethylaniline borane (DEANB) and oxazaborolidine catalyst from sodium borohydride, N,N-diethylaniline hydrochloride and (S)-α,α-diphenylprolinol is described. This protocol is demonstrated successfully to manufacture enantiopure dapoxetine at the plant scale.
- Mahale, Rajendra D.,Chaskar, Sudhir P.,Patil, Kiran E.,Maikap, Golak C.,Gurjar, Mukund K.
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body text
p. 710 - 713
(2012/07/27)
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- Sequential palladium-catalysed C- and N-arylation reactions as a practical and general protocol for the synthesis of the first series of oxcarbazepine analogues
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The first series of oxcarbazepine analogues, starting from readily-available materials and through a high-yielding five-step sequence based on palladium catalysis, is reported. The so-obtained compounds incorporate not only a variety of substituents in both of?the aryl rings comprising the framework of an oxcarbazepine, but also involve the more challenging palladium-catalysed coupling of a number of heteroaromatic substrates. The addition of small amounts of water in some of the metal-catalysed processes showed a beneficial effect, highly increasing the selectivity of such reactions.
- Carril, Mónica,SanMartin, Raul,Domínguez, Esther,Tellitu, Imanol
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p. 690 - 702
(2007/10/03)
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- An advantageous route to oxcarbazepine (Trileptal) based on palladium-catalyzed arylations free of transmetallating agents
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(Chemical Equation Presented) A new route to oxcarbazepine (Trileptal), the most widely prescribed antiepileptic drug, starting from commercially available 2′-aminoacetophenone and 1,2-dibromobenzene, is reported. The sequentially accomplished key steps are palladium-catalyzed intermolecular α-arylation of ketone enolates and intramolecular N-arylation reactions. After several experiments to establish the best conditions for both arylation processes, the target oxcarbazepine is obtained in a satisfactory overall yield, minimizing the number of steps and employing scalable catalytic procedures developed in partially aqueous media.
- Carril, Monica,SanMartin, Raul,Churruca, Fatima,Tellitu, Imanol,Dominguez, Esther
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p. 4787 - 4789
(2007/10/03)
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- Process for the preparation of oxcarbazepine and related intermediates
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A process for preparing Oxcarbazepine III comprising: a) reacting oximinostilbene IV with chlorosulfonyl isocyanate in an inert organic solvent and isolating compound V b) hydrolyzing compound V to form crude Oxcarbazepine III c) purifying oxcarbazepine.
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Page/Page column 3
(2008/06/13)
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- New synthesis of oxcarbazepine via remote metalation of protected N-o-tolyl-anthranilamide derivatives
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Benzyl and allyl protected N-o-tolyl-anthranilamides were efficiently prepared by Buchwald-Hartwig C-N cross coupling reactions, followed by protection of the amino group. Under directed remote metalation conditions, protected dibenzoazepinones were obtained in good yields. Deprotection of the amine and conversion to an urea furnished a new and efficient synthesis of the antiepileptic drug Trileptal.
- Lohse, Olivier,Beutler, Ulrich,Fünfschilling, Peter,Furet, Pascal,France, Julien,Kaufmann, Daniel,Penn, Gerhard,Zaugg, Werner
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p. 385 - 389
(2007/10/03)
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- 3-piperidyl-4-oxoquinazoline derivatives and pharmaceutical compositions comprising the same
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3-piperidyl-4-oxoquinazoline derivatives are provided, which is represented by the formula (I): wherein R represents an amino group or a cyclic amino group such as dibenzoazepine, each of which is substituted with a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or the like, n is an integer of 1 to 3, R3and R4independently represents a hydrogen atom, a lower alkyl group, or the like, or a pharmaceutically acceptable salt thereof. Compounds (I) of the present invention have excellent MTP-inhibitory activity. Thus, these compounds not only inhibit formation of LDL that is a cause of arteriosclerotic diseases but also regulate TG, cholesterol, and lipoproteins such as LDL in the blood and regulate cellular lipids through regulation of MTP activity. They can also be used as a new type of preventive or therapeutic agents for hyperlipemia or arteriosclerotic diseases. Furthermore, they can be used as therapeutic or preventive agents for pancreatitis, obesity, hypercholesterolemia, and hypertriglyceridemia.
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- Process for the preparation of 10-OXO-10, 11-dihydro-5H-dibenz (b,f) azepin-5-carboxamide
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A novel process for the preparation of 10-0×0-10,11-dihydro-5H-dibenz(b,f)azepin-5-carboxamide (VI) consists of starting group 10-methoxy-5H-dibenz(b,f)azepine (IV) and subjecting compound (IV) to direct carbamoylation with isocyanic acid generated in situ from cyanates and acids and then subjecting the product to acid hydrolysis of the enol ether. An alternative process to obtain (VI) starts (IV) effecting the hydrolysis reaction before the carbamoylation. In this case the carbamoylating agent is chlorosulfonyl isocyanate.
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