tert-Butyl isocyanate → 4-[2-(3-tert-Butyl-ureido)-2-phenyl-acetyl]-morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

Participants

Reaction Steps

To a solution of compound 9D (4.0 g, 7.02 mmol) in anhydrous CH2Cl2 (100 mL) was added tert-butyl isocyanate (12D, 3.21 mL, 28.07 mmol). The reaction mixture was stirred at rt overnight. It was concentrated to small volume and purified with silica column chromatography eluting with dichloromethane/EtOAc to give the title compound (13D) as white powder in good yield. 1H NMR (CDCl3, 500 MHz) δ 10.68 (s, 1H), 8.92 (s, 1H), 8.72 (s, 1H), 8.02 (d, 2H, J=8.0 Hz), 7.63 (s, 1H), 7.56 (d, 2H, J=8.0 Hz), 7.38 (s, 5H), 7.19 (d, 1H, J=8.0 Hz), 6.96 (d, 1H, J=8.5 Hz), 5.58 (d, 1H, J=6.0 Hz), 5.30 (s, 1H), 5.18 (d, 1H, J=6.5 Hz), 4.85 (d, 1H, J=11.5 Hz), 4.79 (s, 1H), 3.96 (s, 3H), 3.79 (d, 1H, J=11.5 Hz), 3.62 (br s, 2H), 3.44 (d, 1H, J=10.0 Hz), 3.11 (m, 1H), 1.29 (s, 9H). LCMS (ESI) m/z 669.25 (MH+), 570.23 (100). HPLC: tR=5.22 min.

Provenance & Evidence