Liquid-phase parallel synthesis of combinatorial libraries of substituted 6-carbamoyl-3,4-dihydro-2H-benzo[1,4]thiazines.
In this work, we explored several original combinatorial derivatization patterns for the 3,4-dihydro-2H-1,4-benzothiazine scaffold. The synthesis begins with commercially available 4-chloro- and 4-fluoro-3-nitrobenzoates and employs a sequence of moderate and high-yielding reactions that display a relatively high substituent tolerance. Simple manual techniques for parallel reactions were coupled with easy workup and purification procedures to give high-purity final products. The developed approach was easily adaptable for parallel synthesis of more than 2600 novel 2H-benzo[1,4]thiazine-6-carboxylic acid amides, which were efficiently prepared in a semiautomatic fashion using special CombiSyn synthesizers.
Trifilenkov
Andrey S
AS
Chemical Diversity Research Institute, Khimki, Moscow reg. 114401, Russia.
Kobak
Vladimir V
VV
Salina
Marina A
MA
Kusovkova
Julya A
JA
Ilyin
Alexey P
AP
Khvat
Alexander V
AV
Tkachenko
Sergey E
SE
Ivachtchenko
Alexandre V
AV
D002853:Chromatography, Liquid / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D015394:Molecular Structure; D013843:Thiazines / Q000138:chemical synthesis*
D013843:Thiazines