1-Isocyanato-3-phenoxybenzene → 1-[4-(2,4-Difluorophenoxy)-3-(4-ethoxy-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-3-(3-phenoxyphenyl)urea

Participants

Reaction Steps

A stock solution of Example 1G (0.73 M in pyridine, 458 μL, 0.033 mmol, 1.0 equivalent) and 1-isocyanato-3-phenoxybenzene (0.40 M in DMA, 108 μL, 0.043 mmol, 1.3 equivalents) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 2.32 mL internal volume) set at 100° C., and passed through the reactor at 232 μL min−1 (10 minute residence time). Upon exiting the reactor, the reaction was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (50 mm×21.2 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6.5 min linear gradient 30-70% A, 6.5-7.0 min linear gradient 70-100% A, 7.0-8.5 min 100% A, 8.5-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.56 (s, 1H), 7.45-7.37 (m, 3H), 7.39-7.22 (m, 4H), 7.20-7.12 (m, 1H), 7.11 (ddd, J=8.0, 2.0, 1.0 Hz, 1H), 7.05-6.92 (m, 4H), 6.89 (d, J=8.7 Hz, 1H), 6.63 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 5.82 (s, 1H), 3.92 (q, J=6.9 Hz, 2H), 3.36 (s, 3H), 1.13 (t, J=6.9 Hz, 3H). MS (APCI+) m/z 583.7 (M+H)+.

Provenance & Evidence