A scalable synthesis of an azabicyclooctanyl derivative, a novel DPP-4 inhibitor.
A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.
Fei
Zhongbo
Z
Chemical and Analytical Development, Suzhou Novartis Pharma Technology Co. Ltd, Changshu, Jiangsu, China 215537.
Wu
Quanbing
Q
Zhang
Fei
F
Cao
Yudong
Y
Liu
Chuanqin
C
Shieh
Wen-Chung
WC
Xue
Song
S
McKenna
Joe
J
Prasad
Kapa
K
Prashad
Mahavir
M
Baeschlin
Daniel
D
Namoto
Kenji
K
D000447:Aldehydes / Q000737:chemistry; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002073:Butanes / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007097:Imines / Q000737:chemistry; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry
D000447:Aldehydes; D053961:Azabicyclo Compounds; D002073:Butanes; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007097:Imines; D013452:Sulfonium Compounds; C522016:sulfinimine; C046888:butane