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Simultaneous determination of diastereoisomeric and enantiomeric impurities in ( 1R, 3R )‐1‐(1,3‐benzodioxol‐5‐yl)‐2‐(chloroacetyl)‐2,3,4,9‐tetrahydro‐1h‐pyrido[3,4‐b]indole‐3‐carboxylic acid methyl ester a key intermediate of tadalafil by chiral high‐performance liquid chromatography
Author(s) -
Yu Lushan,
Jin Yiping,
Ye Chun,
Wang Jinzhao,
Hu Gongyun,
Zeng Su
Publication year - 2012
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.21998
Subject(s) - chemistry , enantiomer , chromatography , elution , chirality (physics) , impurity , acetonitrile , indole test , enantiomeric excess , solvent , stereochemistry , enantioselective synthesis , organic chemistry , catalysis , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
( 1R, 3R )‐1‐(1, 3‐Benzodioxol‐5‐yl)‐2‐(chloroacetyl)‐2, 3, 4, 9‐tetrahydro‐1H‐pyrido[3, 4‐b]indole‐3‐carboxylic acid methyl ester (( 1R, 3R )‐Cpe) is a key intermediate used in the synthesis of tadalafil, a highly selective phosphodiesterase type‐5 inhibitor. In the present study, a chiral high‐performance liquid chromatography method was developed for the simultaneous determination of diastereoisomeric and enantiomeric impurities in ( 1R, 3R )‐Cpe. Separation was performed on an Ultron ES‐OVM chiral column (150 mm × 4.6 mm, 5 μm,) with a guard column at a column temperature of 30°C. The gradient elution used was acetonitrile (solvent A) and water (solvent B), and the following elution program was used at a flow rate of 1 ml/min: 0–5 min (80% B), 5–10 min (80–60% B), 10–12 min (60% B). The detection wavelength was 220 nm. The four isomers of Cpe were baseline separated in 12 min. The results of method validation indicated that the method was specific and sensitive and was suitable for the quality control of diastereoisomeric and enantiomeric impurities in ( 1R, 3R )‐Cpe. Chirality, 2012. © 2012 Wiley Periodicals, Inc.