- Benzocycloheptanopyridine compound, and preparation method and application thereof
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The invention belongs to the field of medicines, and particularly relates to a benzocycloheptanopyridine compound, and a preparation method and application thereof, wherein the benzocycloheptanopyridine compound has a structure represented by a formula IV described in the specification. The preparation method comprises the steps: heating magnesium and N-methyl-4-chloropiperidine in a first reaction solvent under the action of an initiator for reaction to obtain a Grignard reagent; carrying out a reaction on 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepto[1,2-b]pyridine-11-one and a Grignard reagent in a second reaction solvent to obtain a compound I; and carrying out a reaction on the compound I in a third reaction solvent under the action of a reducing agent to obtain a compound IV. The benzocycloheptanopyridine compound prepared by the preparation method is high in purity, can detect and monitor the compound IV in the loratadine synthesis process, and is of great significance in improving the quality of loratadine bulk drugs or preparations thereof.
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Paragraph 0082
(2021/07/21)
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- Benzocycloheptanopyridine compound, and preparation method and application thereof
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The invention belongs to the field of medicines, and particularly relates to a benzocycloheptanopyridine compound, and a preparation method and application thereof, wherein the benzocycloheptanopyridine compound has a structure represented by a formula I or a formula IV described in the specification. The preparation method comprises the steps: heating magnesium and N-methyl-4-chloropiperidine in a first reaction solvent under the action of an initiator for reaction to obtain a Grignard reagent; and carrying out a reaction on 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepto[1,2-b]pyridine-11-one and a Grignard reagent in a second reaction solvent to obtain a compound I and a compound IV. The benzocycloheptanopyridine compound prepared by the preparation method is high in purity, can detect and monitor the compound I and the compound IV in the loratadine synthesis process, and is of great significance in improving the quality of loratadine bulk drugs or preparations thereof.
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Paragraph 0081
(2021/07/21)
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- Design and synthesis of thiourea derivatives containing a benzo[5,6]cyclohepta[1,2-b]pyridine moiety as potential antitumor and anti-inflammatory agents
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Thiourea derivatives (6a-e) were developed and screened for antitumor and anti-inflammatory activity. Most of the compounds exhibited growth inhibitory effects comparable to 5-fluorouracil in vitro against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. They also showed stronger anti-inflammatory activity than ibuprofen in vivo in the xylene-induced ear swelling assay in mice.
- Liu, Wukun,Zhou, Jinpei,Zhang, Tong,Zhu, Haiyang,Qian, Hai,Zhang, Huibin,Huang, Wenlong,Gust, Ronald
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scheme or table
p. 2701 - 2704
(2012/05/20)
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- Zinc(II)-catalyzed addition of grignard reagents to ketones
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(Figure presented) The addition of organometallic reagents to carbonyl compounds has become a versatile method for synthesizing tertiary and secondary alcohols via carbon-carbon bond formation. However, due to the lack of good nucleophilicity or the presence of strong basicity of organometallic reagents, the efficient synthesis of tertiary alcohols from ketones has been particularly difficult and, thus, limited. We recently developed highly efficient catalytic alkylation and arylation reactions to ketones with Grignard reagents (RMgX: R = alkyl, aryl; X = Cl, Br, I) using ZnCl2, Me3SiCH 2MgCl, and LiCl, which effectively minimize problematic side reactions. In principle, RMgBr and RMgI are less reactive than RMgCl for the addition to carbonyl compounds. Therefore, this novel method with homogeneous catalytic ZnCl2·Me3SiCH2MgCl·LiCl is quite attractive, since RMgBr and RMgI, which are easily prepared and/or commercially available, like RMgCl, can be applied successfully. As well as ketones and aldehydes, aldimines were effectively applied to this catalysis, and the corresponding secondary amines were obtained in high yield. With regard to mechanistic details concerning β-silyl effect and salt effect, in situ-prepared [R(Me3SiCH2)2Zn] -[Li]+[MgX2]m[LiCl]n (X = Cl/Br/I) is speculated to be a key catalytic reagent to promote the reaction effectively. The simplicity of this reliable ZnCl2·Me 3SiCH2MgCl·LiCl system in the addition of Grignard reagents to carbonyl compounds might be attractive for industrial as well as academic applications.
- Hatano, Manabu,Ito, Orie,Suzuki, Shinji,Ishihara, Kazuaki
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scheme or table
p. 5008 - 5016
(2010/10/04)
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- A PROCESS FOR THE MANUFACTURING OF LORATADINE AND ITS INTERMEDIATES
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The process comprises (i) subjecting substituted benzyl halide to cyanation in a biphasic system using water immiscible solvents by any known methods, (ii) condensing in situ the phenyl acetonitrile thus obtained with nicotinic ester in presence of alkali metal alkoxide and water immiscible organic solvent to produce ketonitrile, (iii) hydrolyzing followed by decarboxylating the said ketonitrile in situ to respective ketone in acid environment below 60° C, (iv) subjecting the ketone so obtained to reduction followed by N-oxidation, cyanation, and hydrolysis by any known methods to produce picolinic acid, (v) cyclising the said picolinic acid to tricyclic ketone by conventional methods, (vi) treating the said tricyclic ketone with organometallic compound containing Mg to produce carbinol, (viii) purifying the said carbinol with purifying agent selected from polar water miscible organic solvent followed by dehydrating with neat sulphuric acid at the temperature below 50° C, to get N-methyl product (olefin), and subjecting the said olefin to N-carbethoxylation to produce loratadine. Loratadine can also be prepared by treating cayano compound with organometallic compound containing Mg to produce a ketone by the methods known in the art followed by cyclising in presence of a mixture of sulfuric acid and a source of boric acid to get N-methyl product and converting to loratadine by N-carbethoxylation.
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Page/Page column 15
(2010/02/15)
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- PROCESS FOR THE PREPARATION OF LORATADINE
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A process for the production of loratadine chemically known as 8-chloro-11-(1-ethoxycarbonyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptal[1,2-B]pyridene has been described. The process comprises reacting a tri-cyclic aromatic ketone with an organometallic compound containing Mg in presence of organic solvent then hydrolyzing and isolating loratadine by conventional methods wherein the reaction between cyclic ketone and the said organometallic compound is effected at a glacial temperature.
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