Efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921.
[reaction: see text] An efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921 was accomplished. Two short enantioselective syntheses of the common key intermediate (S)-alpha-aminoazepinone 6b were developed. Olefin 3 was converted to 6b via asymmetric hydrogenation. Alternatively, enyne 12 was converted to racemic alpha-aminoazepinone 15b, which was transformed to 6b by a practical dynamic resolution.
Singh
Janak
J
Process Research and Development, The Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA. janak.singh@bms.com
Kronenthal
David R
DR
Schwinden
Mark
M
Godfrey
Jollie D
JD
Fox
Rita
R
Vawter
Edward J
EJ
Zhang
Bo
B
Kissick
Thomas P
TP
Patel
Bharat
B
Mneimne
Omar
O
Humora
Michael
M
Papaioannou
Chris G
CG
Szymanski
Walter
W
Wong
Michael K Y
MK
Chen
Chien K
CK
Heikes
James E
JE
DiMarco
John D
JD
Qiu
Jun
J
Deshpande
Rajendra P
RP
Gougoutas
Jack Z
JZ
Mueller
Richard H
RH
D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006865:Hydrogenation; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D001381:Azepines; D004791:Enzyme Inhibitors; D015260:Neprilysin; C478302:gemopatrilat