Hydrochloric Acid → 2-[3-(4,6-Dichloroindol-2-ylmethylamino)prop-1-ylamino]-1H-quinolin-4-one

Participants

Reaction Steps

To ethyl 4,6-dichloroindole-2-carboxylate (0.258 g, 1 mmol) in THF (1 ml) at −78° C. under argon was added 1 ml of a solution of sodium tris(diethylamino)aluminium hydride (prepared from NaAlH4 (1 M in THF, 6 ml) and diethylamine (1.86 ml, 18 mmol), 70 min/0° C.). After 20 min at −78° C. the reaction was allowed to warm to 0° C. over 1 h before addition of 5 M HCl (1.5 ml), water (10 ml) and diethyl ether (50 ml). The phases were separated and the organic layer washed with brine, dried (MgSO4) and evaporated to dryness under reduced pressure to give a pink solid (200 mg; comparison of NMR integrals indicated the presence of approx 40% aldehyde). To this material (132 mg) was added a solution of 0.125 M 2-(3-aminoprop-1-ylamino)-1H-quinolin-4-one in MeOH/HOAc (2 ml, prepared as in example 4a) and sodium cyanoborohydride (0.031 g, 0.5 mmol). After 2.5 h, the reaction mixture was applied to a Varian Bond Elute 1 g SCX cartridge which was flushed with MeOH then eluted with 0.2 M NH3 in MeOH. Product containing fractions were combined and purified by chromatography on silica gel eluting with 0-12% (9:1 MeOH/20 M NH3) in CH2Cl2 to give the title compound, isolated as a colourless solid, (0.050 g, 48%). δH (Methanol-D4) 8.1 (1H, dd, J=8.1, 1.3 Hz), 7.5 (1H, dt, J=1.3, 7.7), 7.2-7.3 (3H, m), 7.0 (1H, d, J=1.6 Hz), 6.5 (1H, s), 5.7 (1H, s), 3.95 (2H, s), (2H, t, J=6.7 Hz), 2.8 (2H, t, J=6.8 Hz), 1.9 (2H, m). MS (ES+) 415, 417 (35%, 25%, MH+), 218 (100%).

Provenance & Evidence