Reaction Steps
A mixture of 6-amino-3-(chloromethyl)-1-(methanesulfonyl)indoline (29) [Tercel, M., Denny, W. A. and Wilson, W. R., Bioorg. Med. Chem. Lett., 1996, in press] (73 mg, 0.28 mmol), 4-nitrobenzaldehyde (51 mg, 0.34 mmol) and toluenesulfonic acid monohydrate (5 mg, 0.3 mmol) in benzene (30 mL) was heated to reflux and most of the benzene slowly distilled off over 40 min. The remaining orange-brown solution was cyanoborohydride (35 mg, 0.56 mmol) then 2N HCl (0.5 mL) were added and the mixture was stirred at 20 C for 40 min, then evaporated. The residue was diluted with water, extracted with EtOAc (×2), and the extracts dried (Na2SO4) and evaporated. Dry column chromatography, eluting with EtOAc/petroleum ether (1:2), gave 3-(chloromethyl)-1-(methanesulfonyl)-6-[(4-nitrobenzyl)amino]indoline (30) as a yellow oil (96 mg, 87%). 1H NMR (CDCl3) a 8.19 (d, J=8.8 Hz, 2 H, ArH o to NO2), 7.52 (d, J=8.8 Hz, 2 H, ArH m to NO2), 7.00 (d, J=8.2 Hz, 1 H, H-4), 6.73 (d, J=2.2 Hz, 1 H, H-7), 6.22 (dd, J=8.2, 2.2 Hz, 1 H, H-5), 4.47 (s, 2 H, NCH2Ar), 4.03 (dd, J=10.8, 8.8 Hz, 1 H, CHHN), 3.92 (dd, J=10.8, 4.6 Hz, 1 H, CHHN), 3.69 (dd, J=10.4, 4.1 Hz, 1 H, CHHCl), 3.67-3.60 (m, 1 H, H-3), 3.53 (dd, J=10.4, 7.9 Hz, 1 H, CHHCl), 2.83 (s, 3 H, NSO2CH3). 13C NMR a 148.7, 147.2, 146.8, 143.4, 119.9 (C-6,8,9,1,4), 127.8, 123.9 (C-2 and 6, 3 and 5), 125.7, 107.9, 98.6 (C-4,5,7), 54.6 (C-2), 47.5, 46.8 (CH2Cl, NCH2Ar), 41.9 (C-3), 34.5 (SO2CH3). MS (DEI, 35Cl) m/z 395 (35%, M+), 346 (100%, M-CH2Cl); HRMS calcd. for C17H18ClN3O4S 395.07066, found 395.06880.
