A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid.
A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.
Wang
Xin
X
Chemical Process R & D, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. xinw@amgen.com
Zhi
Ben
B
Baum
Jean
J
Chen
Ying
Y
Crockett
Richard
R
Huang
Liang
L
Eisenberg
Shawn
S
Ng
John
J
Larsen
Robert
R
Martinelli
Mike
M
Reider
Paul
P