Premium
A Short Synthesis of the Factor‐Xa Inhibitor DX‐9065a using palladium‐catalyzed key steps
Author(s) -
Kehr Christiane,
Neidlein Richard,
Engh Richard A.,
Brandsretter Hans,
Kucznierz Ralf,
Leinert Herbert,
Marzenell Klaus,
Strein Klaus,
Saal Wolfgang Von Der
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800322
Subject(s) - chemistry , cyanation , trifluoromethanesulfonate , palladium , catalysis , cleavage (geology) , stereochemistry , medicinal chemistry , total synthesis , organic chemistry , geotechnical engineering , fracture (geology) , engineering
We describe a new, efficient synthesis of DX‐9065a ( 4 ), a potent inhibitor of the blood coagulation enzyme factor Xa (fXa) which has previously been prepared in more than 20 steps. We saved approximately 10 steps starting with a Pd‐catalyzed cyanation of the triflate 10 of 7‐methoxynaphthalen‐2‐ol ( 9 ). After cleavage of the MeO group with boron tribromide, the triflate 6 was coupled to acrylate 5 in a Heck reaction (→3). The subsequent transformations led to DX‐9065 a.