Gram scale synthesis of the glucuronide metabolite of ABT-724.
A gram scale synthesis of the glucuronide metabolite of ABT-724 is reported. Glycosidic coupling between a trichloroacetimidate glucuronyl donor and a Cbz-protected hydroxypyridylpiperazine glycosyl acceptor is the key step in the synthesis, since attempts to directly glucuronidate the aglycon, aglycon derivatives, and other truncated glycosyl acceptors were unsuccessful. The route was used to produce 2.1 g of metabolite in eight steps from 2-chloro-5-hydroxypyridine in 21% overall yield.
Engstrom
Kenneth M
KM
Global Pharmaceutical R&D, Process Research & Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois 60064-4000, USA. kenneth.engstrom@abbott.com
Daanen
Jerome F
JF
Wagaw
Seble
S
Stewart
Andrew O
AO
D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism; D018491:Dopamine Agonists / Q000737:chemistry / Q000378:metabolism; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism
C521688:2-chloro-5-hydroxypyridine; C487766:ABT724; D001562:Benzimidazoles; D018491:Dopamine Agonists; D004952:Esters; D020719:Glucuronides; D010879:Piperazines; D011725:Pyridines; C014047:hydroxypyridines