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The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst. The coupling reaction provided generally the para-substituted benzoylpyrazoles in the higher yields than the meta-substituted ones. The Boc groups were only utilized as directing functionalities for the benzoylation step and were hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for elimination of the additional deprotection step. [ABSTRACT FROM AUTHOR]

Halogenated aminopyrazoles have rarely been utilized in metal-catalysed cross-coupling reactions mainly due to the complexation of the aminopyrazoles to the metal center, which deactivates the catalyst. In this paper we reveal that the appropriate combination of palladium source and ligand enables efficient Suzuki-Miyaura cross-coupling reactions with even challenging substrates such as halogenated aminopyrazoles. The combination of Pd(OAc)2 and XPhos allowed efficient coupling of halogenated N-acetylaminopyrazoles, whereas XPhos Pd G2 was needed when unprotected aminopyrazoles were used. Generally, the halogenated aminopyrazoles underwent facile cross-coupling reactions with a range of aryl-, heteroaryl-, and styrylboronic acids and esters. The resulting biaryl, bisheteroaryl, or arylalkenyl derivatives were obtained in good-to-high isolated yields. [ABSTRACT FROM AUTHOR]

A catalyst based on the readily available Cu 2 S/TMEDA system using a stable copper(I) source was developed for the Chan-Lam cross-coupling reaction. The capability of the catalyst was demonstrated with 1 H -benzo[ d ]imidazol-2(3 H )-one, 1 H -benzo[ d ]imidazole, and 1 H -imidazole together with electron-deficient, electron-rich, and sterically demanding boronic acids at room temperature in the presence of atmospheric oxygen to give the cross-coupling products in moderate to excellent yields. In addition, the coupling reaction of 1 H -benzo[ d ]imidazole with several pinacol or neopentylglycol boronates indicated further potential of the catalyst. The reaction conditions tolerate the hydroxyl and bromo functional groups. The catalytic system also enables to synthesize the mono-N-substituted anilines from primary aliphatic amines. However, the two model compounds for the secondary and aromatic amines, piperidine and aniline, do not react. Two sterically demanding products with the restricted C N bond rotation, synthesized by the N -arylation of 1 H -benzo[ d ]imidazol-2(3 H )-one with o -tolylboronic acid, enabled to confirm the atropisomers prepared by the Chan-Lam cross-coupling reaction. Furthermore, an example of one-pot Chan-Lam and Suzuki-Miyaura reaction has been reported. [ABSTRACT FROM AUTHOR]