Regioselective synthesis of 4- and 7-alkoxyindoles from 2,3-dihalophenols: application to the preparation of indole inhibitors of phospholipase A2.
An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been developed from commercially available starting materials such as 3-halophenols and 3-chloroanisole. Directed ortho-metalation followed by two palladium-catalyzed processes, a Sonogashira coupling and a tandem amination/cyclization reaction, allows the synthesis of regiochemically pure 4- and 7-substituted indoles. This strategy has been successfully applied to the preparation of 2-[3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yloxy]acetic acid (LY315920), a known inhibitor of phospholipase A2.
Sanz
Roberto
R
Departamento de Química, Area de Química Orgánica, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001-Burgos, Spain. rsd@ubu.es
Castroviejo
M Pilar
MP
Guilarte
Verónica
V
Pérez
Antonio
A
Fañanás
Francisco J
FJ
D000473:Alkanes / Q000138:chemical synthesis*; D000478:Alkylation; D000840:Anisoles / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004987:Ethers / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D013237:Stereoisomerism
C525929:3-chloroanisole; D000473:Alkanes; D000840:Anisoles; D004791:Enzyme Inhibitors; D004987:Ethers; D007211:Indoles; D010636:Phenols; C030374:indole; D010741:Phospholipases A; D054467:Phospholipases A2; D010100:Oxygen