113806-06-7Relevant articles and documents
Preparation method of E-olopatadine
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Paragraph 0040-0045, (2021/03/11)
The invention discloses a preparation method of E-olopatadine, which comprises the following steps: adding [3-(dimethylamino)propyl]triphenylphosphine bromide hydrobromide into a solvent, adding an n-pentane solution of tert-butyl lithium, carrying out heat preservation reaction for 0.5-2 hour, heating to 105-110 DEG C, dropwise adding a toluene solution of methyl 6, 11-dihydro-11-oxo-dibenzo(b, e)oxepine-2-acetate, heating to 105-110 DEG C, stirring for 2-5 hours at the temperature of 105-110 DEG C, then cooling to 0-15 DEG C, carrying out quenching reaction, adding concentrated hydrochloricacid to adjust the pH value to 6+/-0.2, carrying out reduced pressure distillation to dryness to obtain a solid, enabling the solid to pass through a column to obtain an E-olopatadine methyl ester crude product, and carrying out purification. According to the preparation method of Eolopatadine provided by the invention, on the basis of the prior art, key steps are upgraded and transformed, so thatthe reaction steps can be reduced, and the loss is reduced.
PROCESS FOR PRODUCING DIBENZOXEPIN COMPOUND
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Page/Page column 6, (2011/11/13)
A process for producing (Z)-11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid or an acid addition salt thereof, which comprises subjecting 11-hydroxy-11- (3-dimethylaminopropyl)-6,11-dihydrodibenz[b,e] oxepin-2-acetic acid or a salt thereof to a heat treatment in a solvent and a water removal treatment in a reaction system in the presence of an acid selected from a group consisting of hydrogen chloride, sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid, enables the production of (Z)-11-(3-dimethylamino-oropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid or an acid addition salt thereof, which is useful as a medicinal agent, in a high yield and in an industrially advantageous manner.
Synthesis and Antiallergic Activity of 11-(Aminoalkylidene)-6,11-dihydrodibenzoxepin Derivatives
Ohshima, Etsuo,Otaki, Shizuo,Sato, Hideyuki,Kumazawa, Toshiaki,Obase, Hiroyuki,et al.
, p. 2074 - 2084 (2007/10/02)
A new series of 11-substituted 6,11-dihydrodibenzoxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents.These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agents.Most compounds synthesized exhibited potent inhibitory effects on 48-h homogolous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs.Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenzoxepin ring system exhibited inhibitory effects on specific pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific QNB binding to rat striatum muscarinic acetylcholine M1 receptors.Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system.Among the compounds synthesized, (Z)-11--6,11-dihydrodibenzoxepin-2-acetic acid hydrochloride (16) was selected for further evaluation.It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs.Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po.Compound 16 is now under clinical evaluation as KW-4679.
