Methanol → HCID 53477384, compound

Temperature

80 °C

Commercially available 2-fluoro-4-trifluoromethylbenzylamine (0.5 ml, 3.7 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.12 g, 3.7 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (5 ml) of compound 1a (360 mg, 2.4 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 9.5/MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 210 mg of a white solid. Yield=28% 1HNMR (DMSO, 400 MHz) δ 4.42 (2H, d, J=6 Hz), 6.63 (1H, dd, J=8 Hz, J′=1.2 Hz), 6.85 (2H, m), 6.95 (1H, d, J=8 Hz), 7.62 (3H, m), 8.35 (1H, bs), 9.99 (1H, bs), 10.61 (1H, bs); [M+1] 369.1 (C16H12F4N4O2 requires 368.29).

1. additionwas added to the solution
2. customthen evaporated
3. dissolutionthe residue was dissolved in 5 ml of DMF
4. temperaturethe mixture was warmed at 80° C. for 8 hours
5. customThe solvent was evaporated
6. dissolutionthe crude was dissolved in AcOEt (30 ml)
7. washwashed with water (1×20 ml) and brine
8. dry with materialThe organic phase was dried over sodium sulfate
9. concentrationconcentrated under vacuum
10. customThe purification of the crude residue by chromatographic column

ORD record

ord-7cef3fe546d14ca480ab64931069746c

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216975B2