Efficient pyridinylmethyl functionalization: synthesis of 10, 10-Bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (DMP 543), an acetylcholine release enhancing agent.
2-Fluoro-4-methylpyridine (3) is efficiently functionalized by chlorination, hydrolysis and methanesulfonylation into the novel alkylating agent 7. This mesylate is used for the bisalkylation of anthrone under carefully defined conditions to prepare the cognition enhancer drug candidate 1. This process proceeds in up to 37% overall yield and is adaptable for large scale synthesis.
Pesti
J A
JA
Chemical and Physical Sciences Department, The DuPont Pharmaceuticals Company, Experimental Station, Wilmington, Delaware 19880-0500, USA. jaan.a.pesti@dupontpharma.com
Huhn
G F
GF
Yin
J
J
Xing
Y
Y
Fortunak
J M
JM
Earl
R A
RA
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000873:Anthracenes / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans
D000873:Anthracenes; C112296:DMP 543; D000109:Acetylcholine