Hydrogen Peroxide → HCID 135454775, compound

Temperature

5 °C

Hydrogen peroxide (70%; 1.1 mL, ca. 22.6 mmol) was added dropwise to a stirred solution of trifluoroacetic anhydride (3.2 mL, 22.6 mmol) in DCM (15 mL) at 5° C. The solution was stirred at 5° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 5° C. and added to a stirred solution of 1-oxide 8 (597 mg, 2.3 mmol) and trifluoroacetic acid (350 μL, 4.5 mmol) in CHCl3 (15 mL) at 5° C. The solution was stirred at 5° C. for 4 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1,4-dioxide 9 (424 mg, 67%) as a red solid which was dissolved in HCl saturated MeOH, the solvent evaporated and the residue crystallized to give the hydrochloride, mp (MeOH/EtOAc) 170-174° C.; 1H NMR [(CD3)2SO] δ 10.57 (brs, 1 H, NH+Cl−), 8.45 (brs, 1 H, NH), 8.17 (d, J=9.6 Hz, 1 H, H-8), 7.39 (d, J=2.6 Hz, 1 H, H-5), 7.22 (dd, J=9.6, 2.6 Hz, 1 H, H-7), 4.01 (s, 3 H, OCH3), 3.78-3.82 (m, 2 H, CH2N), 3.33-3.37 (m, 2 H, CH2N), 2.82 [d, J=4.5 Hz, 6 H, N(CH3)2]; 13C NMR [(CD3)2SO] δ 165.6, 150.1, 139.7, 125.7,123.4, 119.4, 92.5, 56.8, 54.9, 42.3 (2), 36.0. Anal. Calcd for C12H18ClN5O3.1½H2O: C, 42.1; H, 6.2; N, 20.4. Found: C, 42.0; H, 5.9; N, 20.0%.

1. temperaturewarmed to 20° C. for 10 min
2. temperaturecooled to 5° C.
3. stirringThe solution was stirred at 5° C. for 4 h
4. extractionextracted with CHCl3 (4×50 mL)
5. customThe combined organic fraction was dried
6. customthe solvent evaporated
7. customThe residue was purified by chromatography
8. washeluting with a gradient (0-10%) of MeOH/DCM

ORD record

ord-13b29ee273d54ad29f242af52278903d

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816521B2