- Preparation method of loratadine intermediate 3-[2-(3-chlorphenyl) ethyl]-2-pyridinecarbonitrile
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The invention provides a preparation method as shown in a formula I and a preparation method of 3-[2-(3-chlorphenyl) ethyl]-2-pyridinecarbonitrile. The invention provides a novel method for preparing a loratadine intermediate.
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- Preparation method of loratadine intermediate
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The invention provides a preparation method of a loratadine intermediate, and belongs to the technical field of chemical medicine preparation. The preparation method comprises the following steps: by taking trimethyl-2-cyanopyridine as an initial synthesis raw material, protecting cyano by tert-butyl alcohol to obtain an intermediate 2, performing nucleophilic substitution on the intermediate 2 and benzyl chloride to obtain an intermediate 3, performing deprotection by using phosphorus oxychloride to obtain an intermediate 4, and finally performing addition with a Grignard reagent and obtaining a key intermediate 1 of loratadine under an acidic condition.
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Paragraph 0013; 0017; 0025; 0029; 0031
(2021/04/29)
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- 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; 0049-0051
(2021/02/10)
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- Synthetic method for loratadine intermediate
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The invention specifically relates to a synthetic method for a loratadine intermediate, belonging to the technical field of chemistry. The loratadine intermediate has a structure formula as described in the specification. The synthetic route of the synthetic method is as defined in the specification. The synthetic method is characterized by comprising the following steps: adding a compound 2 in a reaction solvent 1, then adding NCS (N-chlorosuccimide) or NBS (N-bromosuccimide) and an initiator in a reflux state and carrying out a reaction so as to obtain a compound 3; adding the compound 3 into a reaction solvent 2, then adding magnesium powder and iodine and carrying out a reaction under the protection of nitrogen so as to obtain a compound 4; and adding the compound 4 into a reaction solvent 3 and reacting the compound 4 with a compound 5 under palladium-carbon catalysis so as to synthesize a target product 1. The synthetic method provided by the invention avoids usage of hazardous reagents like n-butyllithium and does not need protection of a cyano group at first and then deprotection; and the compound 1 is a key loratadine intermediate, and simplification of synthesis of the intermediate is of important significance to synthesis of loratadine.
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Paragraph 0030; 0031
(2017/08/28)
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- A 3 - [2 - (3 - chlorophenyl) ethyl] - 2 - pyridine carbonitrile preparation method (by machine translation)
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The invention discloses a 3 - [2 - (3 - chlorophenyl) ethyl] - 2 - pyridine carbonitrile (I) of the preparation method. The method in order to 2 - cyano - 3 - methylpyridine and 3 - chlorobenzaldehyde as the starting material, first in an appropriate solvent and condensation reaction under basic conditions shall be 3 - [2 - (3 - chlorophenyl) vinyl] - 2 - pyridine carbonitrile, the intermediate and then the catalytic hydrogenation reaction to obtain 3 - [2 - (3 - chlorophenyl) ethyl] - 2 - pyridine carbonitrile (I); . (by machine translation)
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Paragraph 0026; 0027; 0028
(2018/03/24)
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- Aza-analogue dibenzepinone scaffolds as p38 mitogen-activated protein kinase inhibitors:Design, synthesis, and biological data of inhibitors with improved physicochemical properties
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We recently described a promising novel class of p38 mitogen activated protein (MAP) kinase inhibitors with dibenzepinone-scaffolds. To optimize their physicochemical properties, characterized by calculated log P values and measured lipophilicity (chromatographic hydrophobicity index=CHI), we synthesized aza-analogue dibenzepinones. Here, we present the synthesis and biological data of compounds with the novel aza-dibenzepinone scaffolds. Although these aza-analogues revealed an improved aqueous solubility, introduction of nitrogen was not effective in the p38 MAPK enzyme assay.
- Karcher, Solveigh C.,Laufer, Stefan A.
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supporting information; experimental part
p. 1778 - 1782
(2010/03/01)
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- DIPEPTIDYL PEPTIDASE-IV INHIBITORS
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The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.
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Page/Page column 56-57
(2008/06/13)
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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 14
(2010/02/15)
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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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- 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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- 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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- 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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- ANTIHISTAMINIC 8-(HALO)-SUBSTITUTED 6,11-DIHYDRO-11-(4-PIPERIDYLIDENE)-5H-BENZO[5,6]CYCLOHEPTA[1,2-b]PYRIDINES
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Disclosed are 7- and/or 8-(halo or trifluoromethyl)-substituted-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridines and the pharmaceutically acceptable salts thereof, which possess antihistaminic properties with substantially no sedative properties. Methods for preparing and using the compounds and salts are described
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