2-Cyclobutyloxy-4-methoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile → 4-Amino-5-cyclobutyloxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinoline

Participants

Reaction Conditions

Reaction Steps

Potassium tert-butoxide (810 mg, 0.00725 mol) was added to a solution of 2-cyclobutyloxy-4-methoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylidene-amino}benzonitrile (1.65 g, 0.00363 mol) in 1,2-dimethoxyethane (250 ml) and the reaction stirred at 90° C. under a nitrogen atmosphere for 1 hour. On cooling, the reaction mixture was washed with 1N aqueous citric acid solution (100 ml) and extracted with ethyl acetate (100 ml). The aqueous layer was then basified with 2N aqueous sodium hydroxide solution and extracted with dichloromethane (2×100 ml). These combined organic extracts were dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with a solvent gradient of dichloromethane:methanol:0.880 aqueous ammonia (100:0:0 to 91:9:1 v/v) gave the title compound as a foam (0.93 g, 56%). Rf 0.27 (dichloromethane:methanol:0.880 aqueous ammonia, 97:2:1, v/v). MS m/z 456 (MH)+. 1H-NMR (CDCl3): δ=1.75 (1H, m), 1.92 (1H, m), 2.05 (2H, m), 2.24 (2H, m), 2.54 (2H, m), 3.14 (4H, t), 3.34 (2H, t), 3.57 (2H, t), 3.64 (4H, t), 3.70 (2H, t), 3.88 (3H, s), 3.94 (2H, bm), 4.62 (1H, m), 5.55 (2H, bs), 5.70 (1H, s) 5.96 (1H, s), 6.56 (1H, bs). Found: C, 60.87; H, 7.45; N, 14.79; C24H33N5O4H2O, requires C, 60.67; H, 7.08; N, 14.51%.

Provenance & Evidence