Ammonia → N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide

Temperature

0 °C

H2O2 (70%, 2.8 mL, ca. 56 mmol) was added dropwise to a stirred solution of TFM (7.9 mL, 56 mmol) in DCM (20 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 76 (1.76 g, 5.6 mmol) and TFA (2.2 mL, 28 mmol) in DCM (40 mL) at 0° C. and the solution was stirred at 20° C. for 6 h. Dilute aqueous NH3 solution (40 mL) was added and the mixture stirred vigorously for 30 min and then extracted with DCM (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 (i) starting material 76 (173 mg, 10%); and (ii) 1,4-dioxide 77 (868 mg, 47%) as a yellow solid: mp (MeOH/DCM) 109-110° C.; 1H NMR δ 8.30 (s, 1H, H-9), 8.27 (s, 1H, H-5), 3.44 (br t, J=4.4 Hz, 4H, 2×CH2O), 3.24 (br t, J=7.3 Hz, 2H, CH2), 3.13-3.19 (m, 4H, H-6, H-8), 2.50 (t, J=6.5 Hz, 2H, CH2N), 2.38 (br t, J=4.3 Hz, 4H, 2×CH2N), 2.27 (p, J=7.5 Hz, 2H, H-7), 2.06-2.12 (m, 2H, CH2); 13C NMR δ 155.2, 155.1, 150.5, 139.0, 133.7, 115.8, 113.8, 67.0 (2), 58.0, 53.5 (2), 33.3, 32.8, 28.5, 25.5, 21.8. Anal. calcd for C17H22N4O3: C, 61.8; H, 6.7; N, 17.0. Found: C, 62.0; H, 6.8; N, 17.2%.

1. temperaturewarmed to 20° C. for 10 min
2. temperaturecooled to 0° C
3. stirringthe solution was stirred at 20° C. for 6 h
4. stirringthe mixture stirred vigorously for 30 min
5. extractionextracted with DCM (4×50 mL)
6. customThe combined organic fraction was dried
7. customthe solvent evaporated
8. customThe residue was purified by chromatography
9. washeluting with a gradient (0-10%) of MeOH/DCM

ORD record

ord-af90a27da0ee47e09bc89ed079e3965e

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989451B2