- Preparation method of indacaterol intermediate M
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The invention provides a preparation method of indacaterol intermediate M: 5, 6-diethyl-2, 3-dihydro-1H-indene-2-amine. The preparation method comprises the following steps: by using n-butyraldehyde as an initiator, condensing to obtain a dialdehyde intermediate I, carrying out enolization on the dialdehyde intermediate I to obtain an intermediate II, carrying out D-A reaction on the intermediateII and 3-cyclopentene amine to obtain an intermediate III, and dehydrating to directly obtain a target product. According to the technical scheme, the process is simple, the steps are short, aftertreatment is easy and convenient, and dangerous catalytic hydrogenation is avoided; reaction raw materials are cheap and easily available, and the method is green and energy-saving; the reaction yield ishigh, the product quality is high, and the process cost is low.
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Paragraph 0049-0056
(2020/01/25)
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- Preparation method for indacaterol maleate
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The invention specifically relates to a preparation method for indacaterol maleate, belonging to the field of drug synthesis. The preparation method is simple and short in steps, easy to operate, safe, friendly to environment and fee of an alkaline solution; after a heating reaction, a coupled product in the step 1) can be obtained, and the amount of produced regioisomers, dimers and other by-products is small; the yield of the product indacaterol maleate is high, as high as 93%, and the HPLC purity of the product indacaterol maleate is more than 97.8%; post-treatment is simple, and industrialproduction of indacaterol maleate is facilitated; and the product indacaterol maleate is high in optical purity.
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Paragraph 0063; 0064; 0065
(2018/07/30)
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- The identification of indacaterol as an ultralong-acting inhaled β2-adrenoceptor agonist
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Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of β2-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human β2-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference β2-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.
- Baur, Fran?ois,Beattie, David,Beer, David,Bentley, David,Bradley, Michelle,Bruce, Ian,Charlton, Steven J.,Cuenoud, Bernard,Ernst, Roland,Fairhurst, Robin A.,Faller, Bernard,Farr, David,Keller, Thomas,Fozard, John R.,Fullerton, Joe,Garman, Sheila,Hatto, Julia,Hayden, Claire,He, Handan,Howes, Colin,Janus, Diana,Jiang, Zhengjin,Lewis, Christine,Loeuillet-Ritzler, Frederique,Moser, Heinz,Reilly, John,Steward, Alan,Sykes, David,Tedaldi, Lauren,Trifilieff, Alexandre,Tweed, Morris,Watson, Simon,Wissler, Elke,Wyss, Daniel
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supporting information; experimental part
p. 3675 - 3684
(2010/07/16)
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- 5-HYDROXY-BENZOTHIAZOLE DERIVATIVES HAVING BETA-2-ADRENORECPTOR AGONIST ACTIVITY
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Compounds of formula (I) in free or salt or solvate form, wherein T has the meaning as indicated in the specification, are useful for treating conditions that are prevented or alleviated by activation of the β2-adrenoreceptor. Pharmaceutical co
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Page/Page column 23
(2010/11/08)
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- An efficient and economical synthesis of 5,6-diethyl-2,3-dihydro-1H-inden- 2-amine hydrochloride
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An efficient and economical synthesis of 5,6-diethyl-2,3-dihydro-1H-inden- 2-amine hydrochloride (1) utilizing 2-aminoindan as a cheap and commercially readily available starting material is described. The newly developed synthesis involves six-steps with 49% overall yield, and it introduces two ethyl groups at the 5- and 6-positions via sequential regioselective Friedel-Crafts acetylations and hydrogenations of N-protected-2-aminoindan. The Friedel-Crafts acetylations can be carried out neat with high regioselectivity using acetyl chloride as the reagent as well as the solvent, thus avoiding the use of halogenated solvents.
- Prashad, Mahavir,Hu, Bin,Har, Denis,Repic, Oljan,Blacklock, Thomas J.,Lohse, Olivier
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p. 135 - 141
(2012/12/21)
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