ChemicalBook CAS DataBase List Indacaterol

Indacaterol synthesis

6synthesis methods

Product Name:Indacaterol
CAS Number:312753-06-3
Molecular formula:C24H28N2O3
Molecular Weight:392.49

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It was approved by the European Medicines Agency (EMA) under the trade name Onbrez on November 30, 2009, and by the United States Food and Drug Administration (FDA), under the trade name Arcapta Neohaler, on July 1, 2011. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD) (long-term data in patients with asthma are thus far lacking). It is delivered as an aerosol formulation through a dry powder inhaler.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

Baur, Francois; 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. The Identification of Indacaterol as an Ultralong-?Acting Inhaled β2-?Adrenoceptor Agonist. Journal of Medicinal Chemistry. Volume 53. Issue 9. Pages 3675-3684. Journal. (2010).

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Yield:312753-06-3 97%

Reaction Conditions:

Stage #1: (R)-8-(benzyloxy)-5-[2-[(5,6-diethyl-2,3-dihydro-1H-indole-2-yl)amino]-1-hydroxyethyl]quinolin-2(1H)-onewith 5%-palladium/activated carbon;hydrogen in ethanol at 20; for 2 h;
Stage #2: with 5%-palladium/activated carbon;hydrogen in ethanol at 40; under 757.576 Torr; for 4 h;

Steps:

10 Example 10. Preparation of indacaterol ((R)-2)

A mixture of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)- 1 -hydroxyethylj-8-benzyloxy-( 1H)- quinolin-2-one ((R)-1) (0.42 g, HPLC enantiomeric purity of 99.2% ee), ethanol (50 ml) andRaney nickel (0.5 g) was stirred at 20°C for 2 h. The mixture was filtered and 5% Pd / C (0.05 g) was added to the filtrate. The mixture was stirred under a hydrogen atmosphere at 40°C at the pressure of 101 kPa for 4 h. A TLC analysis of the mixture showed the pure product, therefore the mixture was hot filtered and the residue on the filter was extensively washed with hot ethanol. The filtrate was evaporated in an evaporator at a reduced pressure. The yield was0.33 g (97%) of white powder. HPLC enantiomeric purity 99.0% ee.

References:

WO2014/139485,2014,A1 Location in patent:Page/Page column 10; 11