Triphosgene → 1-(2-(dimethylamino)-4-(trifluoromethyl)benzyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)urea

温度

80 °C

Amine 2a (480 mg, 2.2 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (653 mg, 2.2 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 (10 ml) of compound 1f (320 mg, 1.6 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 1/petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1×30 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 130 mg of a white solid. Yield=19% 1HNMR (DMSO, 200 MHz) δ 2.70 (6H, s), 4.39 (2H, d, J=5.2 Hz), 4.62 (2H, s), 6.48 (1H, dd, J=7.8 Hz, J′=1.2 Hz), 6.81 (1H, t), 7.32 (1H, s), 7.42 (3H, m), 7.72 (1H, dd, J′=1.4 Hz), 8.19 (1H, s), 10.65 (1H, bs); [M+1] 409.1 (C19H19F3N4O3 requires 408.37).

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 (50 ml)
7. washwashed with water (1×30 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レコード

ord-a38a8f04a78e46daa8f20c11f08bb1ca

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09216975B2