3-Aminopropionitrile → 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-yl)propanenitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-1a, step 5, 3.50 g, 8.14 mmol), 3-aminopropionitrile (1.79 mL, 24.4 mmol), diisopropylethylamine (2.84 ml, 16.3 mmol) and Na2CO3 (1.73 g, 16.3 mmol) in dry NMP (4 mL) was heated at 90° C. for 8 hours. The reaction was cooled to room temperature, and then partitioned between EtOAc (100 mL) and water (100 mL), and the layers separated. The organic portion was washed with water (100 mL), saturated aqueous NaHCO3 solution (100 ml), brine (100 mL), dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (SiO2, 0-50% EtOAc in heptane) to furnish 3-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-yl)propanenitrile as a pale yellow foam (2.91 g, 6.28 mmol). LCMS (m/z) 463.1 (MH+), tR=0.98 minute, 1H NMR (CDCl3) δ ppm −0.09 (s, 9H) 0.73-0.85 (m, 2H) 0.99-1.11 (m, 2H) 1.12-1.21 (m, 2H) 1.90-2.05 (m, 1H) 2.75 (t, J=6.7 Hz, 2H) 3.36-3.48 (m, 2H) 3.76 (q, J=6.5 Hz, 3H) 5.50 (br s, 1H) 5.85 (s, 2H) 7.20 (d, J=5.1 Hz, 1H) 8.37 (d, J=5.1 Hz, 1H).

Provenance & Evidence