848946-17-8Relevant articles and documents
Practical asymmetric synthesis of a non-peptidic αvβ 3 antagonist
Keen, Stephen P.,Cowden, Cameron J.,Bishop, Brian C.,Brands, Karel M. J.,Davies, Antony J.,Dolling, Ulf H.,Lieberman, David R.,Stewart, Gavin W.
, p. 1771 - 1779 (2007/10/03)
(Chemical Equation Presented) The development of a practical and highly convergent synthesis of an αvβ3 antagonist is described. The two key fragments present in this compound, a tetrahydropyrido[2,3-b]azepine ring system and a chiral 3-aryl-5-oxopentanoic acid, were constructed independently and then coupled at a late stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde side-chain required for Wittig coupling. The coupling partner was prepared from asymmetric methanolysis of a 3-substituted glutaric anhydride followed by elaboration of the acid moiety to the requisite β-keto phosphorane. Using this route, kilogram quantities of the desired drug candidate were prepared.
