5-(4-Methylpiperazin-1-yl)-2-nitroaniline → 4-(4-Methylpiperazino)-1,2-benzenediamine

A suspension of 5-(4-Methyl-piperazin-1-yl)-2-nitro-phenylamine (513.0 mg, 2.17 mmol) [See Kim, Jung Sun; et al.; J. Med. Chem.; 39; 992 (1996) for the synthesis of this compound] and 10% palladium on carbon (200.8 mg) in ethyl acetate (50 mL) was shaken under 40 psi H2 for 17 hours. The catalyst was removed by filtration through a Celite pad, and the mixture concentrated to afford crude 4-(4-Methyl-piperazin-1-yl)-benzene-1,2-diamine (522 mg) as a yellow foam. This crude diamine was added to a solution of aldehyde 19f (853.7 mg, 2.17 mmol) and elemental sulfur (83 mg, 2.60 mmol) in anhydrous dimethylformamide (40 mL), and the solution heated in an 80° C. oilbath for 6 hours. After cooling to room temperature, the solution was diluted with ethyl acetate (150 mL) and washed with water (50 mL) and saturated aqueous sodium chloride solution (50 mL). The organic layer was dried over magnesium sulfate, filtered, concentrated, and purified by silica gel chromatography (1:20:400 concentrated aqueous NH4OH: EtOH:CH2Cl2), affording 20a (623 mg, 50%) as an orange-brown foam: Rf=0.20 (10% ethanol in dichloromethane); 1H NMR (DMSO-d6) [Some peaks are doubled due to tautomeric isomerization] δ2.23 (s, 3H), 2.49 (m, 4H), 3.10 (m, 4H), 3.71 (s, 3H), 5.80 (s, 2H), 6.91 (m, 4H), 7.36 and 7.47 (2 d, 3H together, J=8.3, 8.7 Hz), 7.64 (d, 1H, J=8.9 Hz), 7.77 (m, 3H), 7.99 (m, 1H), 8.25 (d, 1H, J=7.2 Hz), 8.53 (s, 1H), 8.62 (2 s, 1H together), 9.39 (s, 1H), 12.78 and 12.83 (2 s, 1H together). Anal. (C36H33N7O.0.9 H2O) C, H, N.

1. customThe catalyst was removed by filtration through a Celite pad
2. concentrationthe mixture concentrated

ORD record

ord-cddcfea7e1e343e08afab78d6277787a

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06555539B2