Ammonia → HCID 178526294, compound

Temperature

0 °C

H2O2 (70%, 0.31 mL, ca. 6.3 mmol) was added dropwise to a stirred solution of TFAA (0.88 mL, 6.3 mmol) in DCM (12 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. The solution was added to a solution of 1-oxide 215 (200 mg, 0.63 mmol) and TFA (0.10 mL, 1.4 mmol) in DCM (12 mL) at 0° C. and the solution was stirred at 20° C. for 2.5 h. Dilute aqueous NH3 solution was added until the mixture was basic and then the mixture was extracted with CHCl3 (3×20 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (1-5%) of MeOH/DCM, to give 1,4-dioxide 216 (88 mg, 43%) as a dark yellow solid: mp 150-154° C.; 1H NMR δ 8.28 (t, J=1.6 Hz, 1H, H-9), 7.68 (s, 1H, H-5), 4.87 (t, J=8.5 Hz, 2H, H-7), 3.48 (dt, J=8.5, 1.5 Hz, 2H, H-8), 3.44 (t, J=4.4 Hz, 4H, 2×CH2O), 3.22 (t, J=7.2 Hz, 2H, CH2), 2.49 (t, J=6.5 Hz, 2H, CH2), 2.38 (t, J=4.4 Hz, 4H, 2×CH2N), 2.06-2.13 (m, 2H, CH2); 13C NMR δ 166.7, 156.1, 141.7, 136.3, 130.2, 117.8, 96.1, 73.5, 67.0 (2), 58.0, 53.5 (2), 29.0, 28.8, 21.8. Anal. calcd for C16H20N4O4: C, 57.8; H, 6.1; N, 16.9. Found: C, 57.8; H, 6.1; N, 16.6%.

1. temperaturewarmed to 20° C. for 10 min
2. temperaturecooled to 0° C
3. stirringthe solution was stirred at 20° C. for 2.5 h
4. extractionthe mixture was extracted with CHCl3 (3×20 mL)
5. customThe combined organic fraction was dried
6. customthe solvent evaporated
7. customThe residue was purified by chromatography
8. washeluting with a gradient (1-5%) of MeOH/DCM

ORD record

ord-1d115fd493e741f59d70a75975a53666

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989451B2