title: Synthesis of thiophene-based TAK-779 analogues by C-H arylation.
abstract: A rapid synthesis of thiophene-based TAK-779 analogues 1 is reported using a late-stage diversification strategy. At the end of the synthesis, the key building block 2, which was prepared in six steps from thiophene, was arylated regioselectively at the α-position directly with iodoarenes. Since 2 offers several reactive positions, various established catalyst systems were tested. It was found that Crabtree catalyst (an Ir catalyst) converted efficiently and selectively the thiophene system 2 into 2-aryl-substituted compounds 9. The direct C-H arylation of 2 with electron-rich iodoarenes led to high yields, whereas electron-deficient iodoarenes required longer reaction times for complete conversion. A small set of diverse amides 1 was synthesized by hydrolysis of 9 and subsequent HATU coupling with primary amines 4.
authors: Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Hittorfstraße 58-62, D-48149 Münster, Germany.
authors: Anna
authors: A
authors: Junker
authors: Junichiro
authors: J
authors: Yamaguchi
authors: Kenichiro
authors: K
authors: Itami
authors: Bernhard
authors: B
authors: Wünsch
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D000577:Amides; D000644:Quaternary Ammonium Compounds; D013876:Thiophenes; C119369:TAK 779