2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → n-[2-Fluoro-5-(trifluoromethyl)phenyl]-n'-{6-[2-(4-hydroxytetrahydro-2h-pyran-4-yl)-1,3-thiazol-5-yl]pyridin-3-yl}urea

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Reaction Steps

To a solution of Example 7B (0.042 mg, 0.151 mmol) in tetrahydrofuran (1 mL) was added 2-fluoro-5-trifluoromethylphenyl isocyanate (0.022 mL, 0.151 mmol). After 1 h, the mixture was concentrated under reduced pressure, the residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min) to provide the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.68 (br d, J=12.9 Hz, 2H), 2.07-2.17 (m, 2H), 3.68-3.80 (m 4H), 6.15 (s, 1H), 7.40-7.45 (m, 1H), 7.52 (m, 1H), 7.89 (m, 1H), 8.08 (m, 1H), 8.25 (s, 1H), 8.55-8.60 (m, 2H), 9.10 (s, 1H), 9.40 (s, 1H); MS (ESI) m/z 483 [M+H]+.

Provenance & Evidence