- Preparation method of loratadine
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The invention provides a preparation method of loratadine. The method comprises the following steps: taking 2-cyano-3-methylpyridine as a raw material, and carrying out Ritter reaction, m-chlorobenzylchloride condensation, POCl3 deprotection group, Grignard reaction, cyclization and ethyl chloroformate substitution to obtain 4(8-chlorine-5, 6-dihydro-11H-benzo-[5, 6]cycloheptano[1, 2-b]pyridine-11-subunit)-1-piperidine carboxylic acid ethyl ester. According to the invention, a post-treatment process is innovated, and a new cyclization system is adopted to catalyze the reaction, so that the use of high-cost and high-toxicity strong acid is avoided, and a milder and more economical synthesis method is provided for industrial production.
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Paragraph 0029; 0058-0064
(2021/02/10)
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- Non-innocent Radical Ion Intermediates in Photoredox Catalysis: Parallel Reduction Modes Enable Coupling of Diverse Aryl Chlorides
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We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl radical coupling reactions from abundant but difficult to reduce aryl chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled by a key terminal reductant byproduct, carbon dioxide radical anion.
- Chernowsky, Colleen P.,Chmiel, Alyah F.,Wickens, Zachary K.,Williams, Oliver P.,Yeung, Charles S.
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supporting information
p. 10882 - 10889
(2021/07/31)
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- NEW PROCESS FOR PREPARING LORATADINE FROM A KETONE INTERMEDIATE
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This application is directed to a last step synthetic process for making loratadine from ketone intermediate.
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Page/Page column 9
(2015/06/18)
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- Loratadine and analogues: Discovery and preliminary structure-activity relationship of inhibitors of the amino acid transporter B0AT2
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B0AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B0AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family. Reversible inhibition of B0AT2 was confirmed by electrophysiology. A series of loratadine analogues were synthesized to gain insight into the structure-activity relationships. Our studies provide the first chemical tool for B0AT2.
- Cuboni, Serena,Devigny, Christian,Hoogeland, Bastiaan,Strasser, Andrea,Pomplun, Sebastian,Hauger, Barbara,H?fner, Georg,Wanner, Klaus T.,Eder, Matthias,Buschauer, Armin,Holsboer, Florian,Hausch, Felix
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supporting information
p. 9473 - 9479
(2015/01/09)
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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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experimental part
p. 2701 - 2704
(2012/05/20)
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- PREPARATION OF LORATADINE FORM I
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A process for preparing loratadine crystalline polymorphic Form I.
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Page/Page column 4
(2008/12/07)
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- PROCESS FOR THE PREPARATION OF DESLORATADINE POLYMORPH MIXTURES
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The present application provides a process for the preparation of mixture of polymorphic Form I and Form II of desloratadine in any desired ratio.
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Page/Page column 4-5
(2008/12/09)
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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 17
(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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- PROCESS FOR PREPARING TRICYCLIC COMPOUNDS HAVING ANTIHISTAMINIC ACTIVITY
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Disclosed is a process for preparing a compound having formula (I) wherein R is selected from the group consisting of: alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, and cycloalkyalkyl, R being optionally substituted by substituents selected from halo, -OH, alkyl, alkoxy, or -CF3, said process comprising the following steps: (a) reacting a ketone having formula (A) with a carbanion having formula (B) wherein R is defined above, and R and R are independently selected from the group consisting of -OR and -R; wherein R is alkyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, or substituted cycloalkylalkyl; (b) treating the reaction mixture from step (a) with a protonating agent to form a beta -hydroxy intermediate having formula (C) wherein R, R and R are as defined above; and (c) thermally decomposing the beta -hydroxy intermediate to form the compound of formula (I). The compounds made by this process have antihistaminic activity, e.g., loratadine. Also disclosed is a process for preparing descarboethoxyloratadine, by carrying out the process above, and converting the product to descarboethoxyloratadine. Also disclosed are novel intermediates having formula (II) and (III) wherein R, R and R are as defined above.
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- Process for preparing tricyclic compounds having antihistaminic activity
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Disclosed is a process for preparing a compound having the formula: wherein R1is selected from the group consisting of: alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, and cycloalkylalkyl, R1being optionally substituted by substituents selected from halo, —OH, alkyl, alkoxy, or —CF3, said process comprising the following steps: (a) reacting a ketone having the formula with a carbanion having the formula wherein R1is as defined above, and R2and R3are independently selected from the group consisting of —ORAand —RA, wherein RAis alkyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, or substituted cycloalkylalkyl; (b) treating the reaction mixture from step (a) with a protonating agent; and (c) thermally decomposing the product of 16, to form the compound of formula (I). The compounds made by this process have antihistaminic activity, e.g., loratadine. Also disclosed are novel intermediates having the formula wherein R1, R2and R3are as defined above.
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- Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
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A method of inhibiting Ras function and therefore inhibiting cellular growth is disclosed. The method comprises the administration of a compound of Formula 1.0 Also disclosed are novel compounds of the formulas: Also disclosed are processes for making 3-substituted compounds of the Formulas 1.1, 1.2 and 1.3. Further disclosed are novel compounds which are intermediates in the processes for making the 3-substituted compounds of Formulas 1.1, 1.2, and 1.3.
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- Process for the preparation of loratadine
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The process consists of the reductive coupling between the compounds: 8-chloro-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyridin-11-one (formula VII) and ethyl 4-oxopiperidine-1-carboxylate (formula IV) through the action of low-valent titanium species.
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- Process for the preparation of 10,11-dihydro-5H-dibenzo[A,D]cyclohept-5-enes and derivatives thereof
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5,6-Dihydro-11H-dibenzo[a,d]cyclohept-11-enes are prepared by reacting a dibenzosuberone or an aza derivative thereof with an aliphatic ketone in the presence of low valent titanium.
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- Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
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A method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells is disclosed. The method comprises the administration of a compound of Formula 1.0: STR1 to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being. Novel compounds of formulas 5.0, 5.1 and 5.2, wherein R is --C(R20)(R21)(R46), and 5.3, 5.3A and 5.3B, wherein R is --N(R25)(R48), are disclosed. Also disclosed are processes for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3. Further disclosed are novel compounds which are intermediates in the process for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3.
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- Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
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A method of inhibiting Ras function and therefore inhibiting cellular growth is disclosed. The method comprises the administration of a compound of Formula 1.0 STR1 Also disclosed are novel compounds of the formulas: STR2 Also disclosed are processes for making 3-substituted compounds of the Formulas 1.1, 1.2 and 1.3. Further disclosed are novel compounds which are intermediates in the processes for making the 3-substituted compounds of Formulas 1.1, 1.2, and 1.3.
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- Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
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A method of inhibiting Ras function and therefore inhibiting cellular growth is disclosed. The method comprises the administration of a compound containing a tricyclic ring system to a biological system. In particular, the method inhibits cellular growth in a mammal such as a human being. Novel compounds of the formula: STR1 are disclosed. Also disclosed are processes for making 3-substituted compounds of Formula 4.0. Further disclosed are novel compounds which are intermediates in the processes for making the 3-substituted compounds of Formula 4.0.
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- Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
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Novel compounds of Formula (7.0a), (7.0b) or (7.0c): STR1 are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering a compound of the formula (7.0a), (7.0b) or (7.0c) to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.
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- Bis-benzo or benzopyrido cyclohepta piperidene, piperidylidene and piperazine compounds, compositions and methods of use
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Bis-benzo or benzopyrido piperidene, piperidylidene and piperazine compounds of the formula: STR1 and pharmaceutically acceptable salts thereof are disclosed, wherein Z represents --(C(Ra)2)m --Y--(C(Ra)2)n -- or STR2 The compounds of Formula I possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.
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- Heterocyclic n-oxide derivatives of substituted benzo[5,6]cycloheptapyridines, compositions and methods of use
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Heterocyclic N-oxide derivatives of substituted benzo[5,6]cycloheptapyridines, and pharmaceutically acceptable salts and solvates thereof are disclosed, which possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.
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- Antihistaminic fluoro substituted benzocycloheptapyridines
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Certain benzocycloheptapyridine compounds with fluorine substitution across the exocyclic double bond are prepared and they are useful as antihistaminic agents.
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- 6,11-Dihydro-11-(N-substituted-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-B)pyridines and compositions and methods of use
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Derivatives of 6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine, and pharmaceutically acceptable salts and solvates thereof are disclosed, which possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.
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- N-Substituted 11-(4-piperidylene)-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2 -b]pyridines. Antihistamines with no sedating liability
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Conversion of the basic tertiary amino function of the potent antihistamine, azatadine (Optimine), to neutral carbamate function results in compounds which retain significant antihistamine activity with little or no CNS effects. In guinea pigs the N-ethoxycarbonyl derivative 4 had the same antihistamine potency as terfenadine, a clinically used non-sedating antihistamine. In mice, 4 was a potent antihistamine while lacking CNS effects. The 8-chloro-N-ethoxycarbonyl 5 (loratadine, Sch 29851) was the most potent antihistamine in the series, had no CNS side effects, and was selected for clinical evaluation.
- Villani,Magatti,Vashi,Wong,Popper
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p. 1311 - 1314
(2007/10/02)
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- Tricyclic-substituted piperidine antihistamines
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Antihistamines of the formula STR1 wherein STR2 is a 5 or 6 membered ring which is phenyl or heterocyclic; STR3 is a six membered ring which is 2,3 or 4 pyridyl or is phenyl or substituted phenyl, with the proviso that is STR4 is a nitrogen containing ring, STR5 must be phenyl; Z is an alkylene chain having 0 to 2 carbon atoms in the chain, said 2 carbon chain optionally having one double bond, said chain optionally having either a carbonyl oxygen, or a hydroxy group as a substituent; W is STR6 wherein p is 1 or 2 and n is 1 or 2, R1 is C1 to C6 alkyl, R2 is hydrogen or C1 to C6 alkyl, and the dotted line represents an optical double bond, R2 being absent if the double bond is present, and Y is substituted carboxylate or substituted sulfonyl. Said antihistamines have little or no sedative effects.
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- ANTIHISTAMINIC 11-(4-PIPERIDYLIDENE)-5H-BENZO-[5,6]-CYCLOHEPTA-[1,2-B]-PYRIDINES
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11-(4-Piperidylidene)-5H-benzo-[5,6]-cyclohepta-[1,2-b]-pyridines and their 5,6-dihydro derivatives are disclosed. The compounds are useful as antihistamines with little or no sedative effects.
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