Definition
ChEBI: A monohydroxyquinoline that consists of 5-[(1R)-2-amino-1-hydroxyethyl]-8-hydroxyquinolin-2-one having a 5,6-diethylindan-2-yl group attached to the amino function. Used as the maleate salt for treatment of chronic obstructive pulmonary di
ease.
Side effects
The most commonly reported adverse events associated
with indacaterol treatment were nasopharyngitis, upper respiratory
tract infection, and headache and cough following inhalation. Adverse
events were mild or moderate in most cases, and became less frequent
with continued treatment.
Synthesis
The chemical synthesis of indacaterol begins
with a-chlorination of 5-acetyl-8-benzyloxy-2-quinolone with benzyltrimethylammonium
dichloro-iodate. The resultant chloroketone is
reduced with borane in tetrahydrofuran in the presence of the chiral
boron catalyst R-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2c][
1,3,2]oxazaborole to produce the corresponding chlorohydrin intermediate
in high enantiomeric excess. The chlorohydrin intermediate is
cyclized to the corresponding epoxide by treatment with potassium
carbonate, the epoxide is condensed with 5,6-diethylindan-2-amine,
and the benzyl protecting group is removed by hydrogenolysis to
produce indacaterol. The 5,6-diethylindan-2-amine intermediate is
derived from 1,2-diethylbenzene via Friedel-Crafts acylation
with 3-chloropropionyl chloride, cyclization of the resultant 3-chloro-
1-(3,4-diethylphenyl)-1-propanone by means of concentrated sulfuric acid to 5,6-diethylindan-1-one, oximation with butyl nitrite, and reduction
of the oxime to an amine via treatment with hydrogen over palladium-
carbon.
