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Synthesis 2009(6): 913-920  
DOI: 10.1055/s-0028-1087970
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Parallel Synthesis of Drug-like 5-Amino-Substituted 1,2,4-Thiadiazole Libraries Using Cyclization Reactions of a Carboxamidine Dithiocarbamate Linker

Joo Yeon Parka,b, In Ae Ryua,b, Ji Hoon Parka, Duck Chan Hab, Young-Dae Gong*a
a Center for High Throughput Synthesis Platform Technology, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejon 305-600, Korea
b Department of Chemistry, Korea University, Sungbuk-gu, Seoul 136-701, Korea
Fax: +82(42)8607698; e-Mail: ydgong@krict.re.kr;
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Publikationsverlauf

Received 14 October 2008
Publikationsdatum:
24. Februar 2009 (online)

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Abstract

A general method has been developed for the solution-phase parallel synthesis of various drug-like 5-amino-substituted 1,2,4-thiadiazole derivatives, which employs initial cyclization reaction of carboxamidine dithiocarbamate 2 with p-toluenesulfonyl chloride. The carboxamidine dithiocarbamate 2 was produced by a three-component nucleophilic substitution reaction between carbon disulfide, benzamidine 1, and benzyl chloride. The key intermediate in this sequence, 5-(benzylsulfanyl)-3-phenyl-1,2,4-thiadiazole (3), is then transformed to the desired 5-amino-substituted 3-phenyl-1,2,4-thiadiazoles 6 in good yields and purities via oxidation of the sulfide group to form the corresponding sulfone followed by substitution reactions with various amines.

Key words

parallel synthesis - drug-like properties - 5-amino-1,2,4-thiadiazole - dithiocarbamate linker

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