Chlorinated thiophenes. Part 2. Trihalogenated hydroxythiophenes; preparation, reactions and tautomeric properties

The Discovery of 4-{1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic Acid (MK-2894), A Potent and Selective Prostaglandin E2 Subtype 4 Receptor Antagonist

“…The thiophenecarboxylic acids 19 and 20 were obtained using similar procedures described for the transformation of alcohol 7 to acid 9 in Scheme . To prepare the 2,5-dichlorothiophene-containing analogues 27 , the desired carboxylic acid 21 was obtained by the treatment of the 2,5-unsubstituted precursor 19 with NCS in hot acetic acid . Compounds 26 − 28 were obtained from acids 19 − 21 in a similar manner as described in Scheme using enantiomerically pure ( S )-α-methylbenzylamine 22…”

Efficient Methods for the Synthesis of Thieno[3,2-b]thiophene and Thieno[3,2-b]furan Derivatives

“…The direction of the reaction depends on the structure of the starting hydroxythiophene, the nature of the alkylating agent, and the base employed. [20][21][22] Recently, we have found that the alkylation of hydroxythiophene 1 with ahalo ketones is strongly dependent on the polarity of the solvent. 23 The C-alkylated products 2a-d were obtained in high yields when the reaction was carried out in benzene in the presence of metallic sodium.…”