Addition of benzylic and allylic organozinc and Grignard reagents to resin-bound imines to provide alpha-branched secondary amines bearing a wide variety of functional groups. Utility in the synthesis of beta-3 adrenergic receptor agonists.
Benzylic and allylic organozinc and Grignard reagents have been added to resin-bound imines to provide alpha-branched secondary amines. Many functional groups, including electrophilic groups, were compatible with this methodology. Three modules--a resin-bound primary amine, an aromatic aldehyde, and the organometallic--were independently varied to produce a combinatorial library of alpha-branched secondary amines designed as beta-3 adrenergic receptor agonists.
Wu
Gang
G
Bristol-Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543, USA.
Cai
Zhen-Wei
ZW
Bednarz
Mark S
MS
Kocy
Octavian R
OR
Gavai
Ashvinikumar V
AV
Godfrey
Jollie D
JD
Washburn
William N
WN
Poss
Michael A
MA
Sher
Philip M
PM
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001554:Benzene / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000588:Amines; D007097:Imines; D015032:Zinc; D001554:Benzene