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A Highly Efficient Synthesis of a Naphthalenoid Histamine‐3 Antagonist
Author(s) -
Ku YiYin,
Grieme Tim,
Pu YuMing,
Bhatia Ashok V.
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200900162
Subject(s) - chemistry , regioselectivity , hydroamination , yield (engineering) , combinatorial chemistry , histamine , suzuki reaction , antagonist , catalysis , coupling reaction , stereochemistry , organic chemistry , palladium , receptor , medicine , biochemistry , materials science , metallurgy
A highly efficient synthesis of the potent and selective histamine‐3 receptor antagonist 1A was accomplished in four chemical steps and a salt formation step in 36% overall yield from 6‐bromo‐2‐naphthalenol 9 . The key features are a regioselective Suzuki coupling protocol for selective vinylation of 12 with potassium vinyltrifluoroborate in high yield (92%) with excellent regioselectivity (90:2) and a base‐catalyzed hydroamination reaction of 11 in an anti‐Markovnikov fashion under mild reaction conditions. An optimized copper‐catalyzed cross coupling reaction is used to incorporate the pyridazinone 4 .