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.
Chemical and Analytical Development, Suzhou Novartis Pharma Technology Co. Ltd, Changshu, Jiangsu, China 215537.
Zhongbo
Z
Fei
Quanbing
Q
Wu
Fei
F
Zhang
Yudong
Y
Cao
Chuanqin
C
Liu
Wen-Chung
WC
Shieh
Song
S
Xue
Joe
J
McKenna
Kapa
K
Prasad
Mahavir
M
Prashad
Daniel
D
Baeschlin
Kenji
K
Namoto
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