<i>N</i>-(6-Chloro-3-nitropyridin-2-yl)-5-(1-methyl-1<i>H</i>-pyrazol-4-yl)isoquinolin-3-amine

Abstract

Here we describe the synthesis of N-(6-chloro-3-nitropyridin-2-yl)5-(1-methyl-1H-pyrazol-4-yl)isoquinolin-3-amine via a three-step procedure including a Buchwald–Hartwig arylamination with benzophenone imine and a highly regioselective nucleophilic aromatic substitution. The title compound was analyzed by nuclear magnetic resonance spectroscopy (1H, 13C, HSQC, HMBC, COSY, DEPT90 and NOESY), high resolution mass spectrometry (ESI-TOF-HRMS) and infrared spectroscopy (ATR-IR) and its structure was confirmed by single crystal X-ray diffraction. The inhibitory potency of the title compound was evaluated for selected kinases harboring a rare cysteine in the hinge region (MPS1, MAPKAPK2 and p70S6Kβ/S6K2).

Keywords

• 3-nitropyridines
• nucleophilic aromatic substitution
• Buchwald–Hartwig arylamination
• protein kinase inhibitors
• covalent inhibitors