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

Temperature

0 °C

H2O2 (70%, 3.6 mL, ca. 72 mmol) was added dropwise to a stirred solution of TFAA (10.2 mL, 72 mmol) in DCM (25 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. and added to a stirred solution of 1-oxide 62 (2.48 g, 7.2 mmol) and TFA (2.8 mL, 36 mmol) in DCM (25 mL) at 0° C. The solution was stirred at 20° C. for 16 h, cooled to 0° C. and made basic with dilute aqueous NH3 solution and stirred vigorously for 30 min. The mixture was 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 (i) starting material 62 (981 mg, 40%) and (ii) 1,4-dioxide 63 (504 mg, 19%) as a red solid: mp (MeOH) 140-141° C.; 1H NMR δ 8.09 (s, 2H, H-5, H-9), 7.32 (br s, 1H, NH), 3.74 (br t, J=4.6 Hz, 4H, 2×CH2O), 3.57-3.63 (m, 2H, CH2N), 3.09 (br t, J=7.5 Hz, 2H, H-6), 3.05 (br t, J=7.5 Hz, 2H, H-8), 2.50-2.55 (m, 4H, 2×CH2N), 2.47 (br t, J=7.1 Hz, 2H, CH2N), 2.20 (p, J=7.5 Hz, 2H, H-7), 1.71-1.79 (m, 2H, CH2), 1.61-1.69 (m, 2H, CH2); 13C NMR δ 155.9, 149.5, 145.8, 137.9, 129.8, 115.7, 111.6, 66.6 (2), 58.1, 53.5 (2), 41.2, 33.4, 32.4, 27.1, 25.5, 23.4; HRMS (FAB+) calcd for C18H26N5O3 (MH+) m/z 360.2036, found 360.2039.

1. temperaturewarmed to 20° C. for 10 min
2. temperaturecooled to 0° C.
3. stirringThe solution was stirred at 20° C. for 16 h
4. temperaturecooled to 0° C.
5. stirringstirred vigorously for 30 min
6. extractionThe mixture was extracted with CHCl3 (4×50 mL)
7. customthe combined organic fraction was dried
8. customthe solvent evaporated
9. customThe residue was purified by chromatography
10. washeluting with a gradient (0-10%) of MeOH/DCM

ORD record

ord-2548d32254fc4f0497a08df50f21ea65

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989451B2