- Synthetic method of epinastine hydrochloride
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The invention relates to a synthesis method of epinastine hydrochloride. The method comprises the following steps: reacting phthalic anhydride with aniline to obtain a compound 1, reacting the compound 1 with polyphosphoric acid under certain conditions to perform cyclization to obtain a compound 2, reducing carbonyl of the compound 2 under certain conditions to obtain a compound 3, and carrying out chlorination reaction on the compound 3 to obtain a compound 4, carrying out cyano substitution reaction on the compound 4 to obtain a compound 5, reducing the compound 5 by using a carbon-nitrogenunsaturated bond to obtain a compound 6, reacting the compound 6 with cyanogen bromide, and forming hydrochloride by using hydrochloric acid to obtain a compound 7; according to the method, the epinastine hydrochloride is prepared from bulk chemical products, is extremely low in price and mild in reaction condition, avoids the use of azide compounds, and the method is suitable for large-scale industrial production. The prepared epinastine hydrochloride is high in purity and low in cost, and has higher market competitiveness.
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Paragraph 0041-0042
(2020/12/15)
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- A Modular Approach to Dibenzo-fused ?-Lactams: Palladium-Catalyzed Bridging-C?H Activation
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Tricyclic ring systems possessing a dibenzo structure joined to a seven-membered heterocyclic ring frequently show important biological activities. However, a modular approach to these molecules based on efficient intermolecular reaction of readily available chemicals is lacking. Herein, an unprecedented palladium-catalyzed formal [4+3] annulation for modular construction of these tricyclic systems is described. This reaction features easily accessible reactants (o-haloarylaldehydes and N-tosylhydrazones), broad substrate scope, and excellent functional group compatibility. The synthetic potential is demonstrated by the easy scale-up reactions, late-stage modification of complex molecules, and collective synthesis of bioactive molecules and approved drugs.
- Huang, Xueliang,Ma, Liyao,Xia, Jiajin,Xin, Luoting,Yu, Yinghua,Zhu, Lei
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p. 18261 - 18266
(2020/08/21)
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- A synthesis method of epinastine hydrochloride
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The invention discloses a synthesis method for epinastine hydrochloride. With a compound (6-aminomethyl-6,11-dihydro-5H-dibenzo [b, e] azepine maleate), shown in the formula II, being the initial raw material, epinastine hydrochloride is synthesized. By the utilization of the synthesis method for epinastine hydrochloride, epinsastine hydrochloride can be effectively synthesized, and the method has the advantages of being high in synthesis efficiency, safe in production, simple in technology operation, short in production period and the like and is more suitable for large-scale and industrialized production of epinastine hydrochloride.
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Paragraph 0061; 0063; 0064; 0068
(2018/12/13)
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- Synthesis method of epinastine hydrochloride
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The invention discloses a synthesis method of epinastine hydrochloride and relates to the technical field of medicines. The synthesis method comprises the following steps of: adopting 6-cyano-6,111H-dibenzo[b,e]azacycloheptatriene as a raw material, under the existence of RaneyNi, adopting methanol solution of ammonia as a solvent, introducing hydrogen to generate reduction reaction, and then obtaining 6-(aminomethyl)-6,11-dihydro-1H-dibenzo[b,e]azacycloheptatriene; leading the 6-(aminomethyl)-6,11-dihydro-1H-dibenzo[b,e]azacycloheptatriene and cyanogen bromide to generate cyclization reaction, then using alkaline for neutralization, and obtaining 3-amino-9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5a]azacycloheptatriene; leading the 3-amino-9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5a]azacycloheptatriene and hydrochloric acid to form a salt, and obtaining the epinastine hydrochloride. The synthesis method disclosed by the invention has the beneficial effects that in the reduction step, the RaneyNi is adopted as a catalyst, catalytic hydrogenation reaction is carried out in the methanol solution of the ammonia, the reaction conditions are moderate, the reaction time is shorter, the yield of reduction products can reach 90% or more, the whole synthesis process is stable, the reaction steps are simple, the consumed time is short and the prepared epinastine hydrochloride is high in purityand yield.
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Paragraph 0027-0029; 0032-0034; 0037-0039; 0042-0044
(2018/09/08)
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- A 6 - aminomethyl - 6, 11 - dihydro - 5H - dibenzo [b, e] for the preparation method
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The invention relates to a preparation method of 6-aminomethyl-6,11-dihydro-5H-dibenzo[b,e]azepine, and belongs to the technical field of drug synthesis. The preparation method comprises the following steps: (1) converting phenylglycine methyl ester hydrochloride into benzene ammonia amide through amidation reactions; (2) converting benzene ammonia amide into 2-((2-amino-2-oxo-phenethyl)amino)methyl benzoate through coupling reactions; (3) converting 2-((2-amino-2-oxo-phenethyl)amino)methyl benzoate into 2-((2-(hydroxymethyl)phenyl)amino)-2-phenyl acetamide through reduction reactions; (4) converting 2-((2-(hydroxymethyl)phenyl)amino)-2-phenyl acetamide into 6-aminomethyl-6,11-dihydro-5H-dibenzo[b,e]azepine through alkylation reactions. The provided preparation method has the advantage that no cyanide is used.
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- Synthetic method of epinastine hydrochloride
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The invention discloses a synthetic method of epinastine hydrochloride. The synthetic method comprises the following steps: enabling a substance A to react with a substance B to obtain a substance C; enabling the substance C to be subjected to ring closing reaction with polyphosphoric acid to obtain a substance D; enabling the substance D to react with a de-protection reagent to obtain a substance E; enabling the substance E to react with cyanogen bromide to obtain epinastine and then salifying with hydrochloric acids to obtain the epinastine hydrochloride. The synthetic method disclosed by the invention is easily-available in raw materials, mild in reaction conditions, low in energy consumption, low in production cost, simple to operate, short in preparation period and suitable for large-scale industrial production; the prepared epinastine hydrochloride is high in purity and relatively high in yield in each step of reaction.
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Paragraph 0093; 0096; 0120
(2017/10/27)
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- Synthetic method of epinastine hydrochloride impurity B
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The invention relates to the field of pharmaceutical technology and, and particularly relates to a preparation process of an epinastine hydrochloride impurity. The method comprises: firstly, using 6-(phthalimidomethyl)-6,11-dihydro-5H-dibenz[b,e]azepine (shown in the description) as a starting material, removing a protective group with hydrazine hydrate and then performing ring closure with cyanogen bromide to obtain 3- amino-9,13-dihydro-1H-dibenzo [c,f ]-imidazo [1,5-a] heterocyclic nitrogen (shown in the description) (epinastine), and finally reacting with a simple substance bromine to obtain the epinastine hydrochloride impurity B. The synthetic method of the epinastine hydrochloride impurity B has the advantages of being simple in process route, convenient to operate, good in selectivity and high in yield. The synthetic epinastine hydrochloride impurity B can be used as a control substance for testing a related substance of epinastine hydrochloride, can be applied in quality control of epinastine hydrochloride and related preparations thereof, and can be used for controlling the purity of the epinastine hydrochloride active pharmaceutical ingredients or preparations thereof.
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Paragraph 0026-0029
(2017/09/12)
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- A new process for the preparation of 3-amino-9,13b-dihydro-1H-dibenz [c,f] imidazo[1,5-a]azepine bromic acid salt
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The present invention relates to a novel method for preparing an enhanced 3-amino-9, 13b-dihydro-1H-dibenz [c,f] imidazo [1,5-a] azepine bromic acid salt. The compound is used as an intermediate in manufacturing the epinastine hydrochloride. The compound is represented by the structural formula (I).COPYRIGHT KIPO 2015
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Paragraph 0017; 0047-0049; 0051-0053
(2016/12/07)
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- NOVEL CRYSTAL MODIFICATION OF EPINASTINE OR SALTS THEREOF AND PROCESS FOR PREPARATION THEREOF
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The present invention provides novel crystalline forms of 3-amino-9,13b-dihydro-lH- dibenzo[c,f]imidazo[l55-a] azepine or salts thereof and process for preparation thereof.
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Page/Page column 24
(2009/06/27)
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- New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine
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A series of new tetracyclic guanides were synthesized by various methods. Specific binding of the described compounds to histamine-1 and histamine-2 receptors was determined. The compound 3-amino-9, 13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine (epinastine, WAL 801) combines high selectivity with high affinity for the H1 receptor and was selected from the compounds studied for further pharmacological and clinical investigations. Experimentally determined physicochemical parameters (pk(a)-value, partition coefficient) and the hydrogen-bonding ability of epinastine are indications that this compound will not easily cross the blood-brain barrier. This explains the absence of CNS side-effects of epinastine in pharmacological and clinical studies.
- Walther,Daniel,Bechtel,Brandt
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p. 440 - 446
(2007/10/02)
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