312753-70-1Relevant articles and documents
Preparation method of indacaterol intermediate M
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Paragraph 0049-0056, (2020/01/25)
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.
The identification of indacaterol as an ultralong-acting inhaled β2-adrenoceptor agonist
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
supporting information; experimental part, p. 3675 - 3684 (2010/07/16)
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.
An efficient and economical synthesis of 5,6-diethyl-2,3-dihydro-1H-inden- 2-amine hydrochloride
Prashad, Mahavir,Hu, Bin,Har, Denis,Repic, Oljan,Blacklock, Thomas J.,Lohse, Olivier
, p. 135 - 141 (2012/12/21)
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.
