Dichloromethane → (S)-tert-butyl 1-(4-(4-(2-chloro-3-(propylsulfonamido)phenyl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

Participants

Reaction Steps

To a mixture of (S)-tert-butyl 1-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (I-1a, 256 mg, 0.45 mmol), N-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propane-1-sulfonamide (SM-10, 292 mg, 0.81 mmol), aqueous 2.0 M Na2CO3 solution in DME (4 mL) was added PdCl2(dppf).DCM. The reaction vial was sealed and irradiated at 120° C. for 10 minutes in a microwave reactor. LCMS indicated complete conversion and the reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with EtOAc (2×). The combined organic portions were washed with water, brine, dried (Na2SO4), and concentrated to furnish a dark red oil. Purification by flash chromatography (SiO2, 50-100% EtOAc in heptane) provided (S)-tert-butyl 1-(4-(4-(2-chloro-3-(propylsulfonamido)phenyl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (4A-1: 116 mg, 0.14 mmol) as a yellow oil: LCMS (m/z) 720.3, (MH+), tR=1.03 minutes.

Provenance & Evidence