Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists.
The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.
Hartner
Frederick W
FW
Department of Process Research, Merck Research Laboratories, Rahway, NJ 07065, USA. fred_hartner@merck.com
Hsiao
Yi
Y
Eng
Kan K
KK
Rivera
Nelo R
NR
Palucki
Michael
M
Tan
Lushi
L
Yasuda
Nobuyoshi
N
Hughes
David L
DL
Weissman
Steven
S
Zewge
Daniel
D
King
Tony
T
Tschaen
Dave
D
Volante
R P
RP
D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
C496034:3-((7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine; C496033:3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine; D039302:Integrin alphaVbeta3; D009287:Naphthyridines; D011407:Propane