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The synthesis of novel pyrazolothienopyridinone derivatives as potential GABAA receptor modulators was performed and is herein described. A crucial step of the synthesis involving handling unstable aminothiophenes was managed via two different synthetic strategies delivering a set of 8 target compounds. [ABSTRACT FROM AUTHOR]

Suzuki-Miyaura cross-coupling reactions between heteroaryl bromides and arylboronic acids were performed employing a continuous-flow approach using a simple flow reactor designed in-house. Pd(PPh3)4 was used as catalyst, and arylboronic acids containing both electron-withdrawing and electron-donating groups were applied. The coupling process required 23 minutes of residence time to be completed and generally good yields were obtained. Subsequent arylation of 2-phenyl pyridine was carried out via a C-H activation strategy using substituted bromobenzene compounds and a ruthenium(II) catalyst. To the best of our knowledge in this work we present for the first time the possibility of performing intermolecular C-H activation in a continuous-flow system. [ABSTRACT FROM AUTHOR]

Polysubstituted imidazoles represent a common structur-al motif in bioactive molecules. A modular and flexible strategy to-wards 2,4,5-triarylated imidazoles is reported applying a Suzuki-Miyaura cross-coupling protocol. Employing 1-protected 2,4,5-tri-bromoimidazole as starting material, both stepwise and one-pot pro-tocols towards the title compounds are disclosed. The utility of the approach was demonstrated by synthesizing neurodazine, a biolog-ically active molecule affecting neuronal cell differentiation. [ABSTRACT FROM AUTHOR]

The direct arylation of N-(2-pyridyl) substituted anilines is described. Arylation takes place in ortho position to the amine functionality and is directed by the pyridine N-substituent. Remarkably, N-arylation was never observed as a competing process even though conditions also suitable for Buchwald-Hartwig reactions were applied. The scope of the reaction was investigated in terms of aryl donors as well as the electronic nature of the substrate. Good yields were obtained for most examples through an operationally simple procedure, which did not require inert conditions or even glove box techniques. Pd(OAc)2 was applied as a cheap catalyst and boronic acids as readily available aryl donors. To obtain full conversion, 1,4-benzoquinone and a silver salt (e.g., Ag2O) were required as additives and reacted at relatively mild temperatures (e.g., 80 °C). Additionally, the pyridine-directing group was cleaved after the reaction to give ortho-arylated aniline derivatives. [ABSTRACT FROM AUTHOR]

The selective C-N cross-coupling of 2-fluoro-4-iodopyr�idine with aromatic amines is reported. In contrast to conventional substitutions where C-N bond formation takes place at the 2-position (e.g., 2,4-dichloropyridine), the Buchwald-Hartwig cross-�coupling was found to be complementary and exclusive for the 4-position. Reactions were carried out under microwave irradiation typically within 30 minutes. These conditions also allowed a decrease in the amount of base required to 3.5 equivalents compared to 20 equivalents in established protocols. Additionally, use of potassium carbonate as a mild base was sufficient, and good yields of the coupling products were obtained in all cases with the simple system Pd(OAc)2/BINAP. [ABSTRACT FROM AUTHOR]

Abstract: A microwave assisted Buchwald–Hartwig amination protocol is reported for a series of dihalopyridine precursors. Using this procedure, selective substitution of one halogen by aryl or alkylamines is possible in very short time, usually 30 min. Mild base (K2CO3) can be used successfully, which broadens the substrate scope. The second halogen can then be substituted using alkylamines under nucleophilic substitution condition or via a Suzuki–Miyaura cross-coupling reaction. The target compounds are potential inducers of cardiomyogenesis as innovative approach in regenerative medicine. [Copyright &y& Elsevier]

Abstract: A series of N-arylthiazole-2-amines was prepared and their biological activity for the promotion of skeletal muscle cell differentiation was investigated, a process of significant importance in muscle regeneration. A versatile new synthetic route towards the target compounds was developed and the substrate scope of this methodology was investigated. Introduction of the 2-aminoaryl substituent was carried out via nucleophilic substitution reactions in excellent yields. Furthermore, the aryl in 5-position was introduced applying a direct arylation reaction, a major improvement compared to reported synthetic routes regarding atom efficiency and sustainability. [Copyright &y& Elsevier]