3-(Trifluoromethyl)phenyl isocyanate → acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester

Beteiligte Stoffe

Reaktionsschritte

LHMDS (1.0 M in THF, 7.68 mL, 7.68 mmol) is added over 1 min to a solution of (4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidin-2-yl)methyl acetate (1.21 g, 3.84 mmol) and 1-isocyanato-3-(trifluoromethyl)benzene (0.70 mL, 5.08 mmol) in THF (40 mL) at −78° C. for 40 min. Saturated aqueous NH4Cl (100 mL) and water (20 mL) are added and the mixture is extracted with EtOAc (3×60 mL). The combined organic layers are washed with brine (30 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (0-100% EtOAc/heptane) to give acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester. MS (ESI) m/z 503.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.99 (s, 1 H)8.68 (d, J=5.81 Hz, 1 H)8.12 (s, 1 H)7.92 (d, J=7.83 Hz, 1 H)7.66 (t, J=8.08 Hz, 1 H)7.51-7.55 (m, 2 H)7.11-7.18 (m, 2 H)6.64 (s, 1 H)5.02 (s, 2 H)2.59 (s, 3 H)1.88 (s, 3H).

Herkunft & Nachweise