Dimethylformamide → 4-[Bis(2-chloroethyl)amino]phenyl-3-[6-methoxy-2-(4-methoxyphenyl)quinolin-4-yl]urea

Beteiligte Stoffe

Reaktionsschritte

To a solution of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.918 g, 3.0 mmol) in dry CHCl3 (35 mL) containing Et3N (0.6 mL) was added dropwise a solution of triphosgene (356 mg, 1.2 mmol.) in an ice bath with vigorous stirring for 30 min. The reaction mixture was evaporated and the residue diluted with THF (20 mL), filtered through a pad of Celite, washed with THF (5 mL). This intermediate was dissolved in anhydrous DMF (1 mL) and then added dropwise to a solution of 4-amino-6-methoxy-2-(3-methoxyphenyl)quinoline (280 mg, 1.0 mmol) in dry DMF (1 mL). The reaction mixture was stirred at 50° C. for 9 h and the solvent was removed by vacuum distillation. The residue was chromatographed on a silica gel column (2×24 cm) using CHCl3/MeOH/(100:1 v/v) as eluent. The fractions containing the desired product were combined, evaporated and the solid residue was recrystallized from EtOH to give 1-{4-[bis(2-chloroethyl)amino]phenyl-3-[6-methoxy-2-(4-methoxyphenyl)quinolin-4-yl]urea (BO-1049); 400 mg (74.2%); mp 112-113° C.; 1H NMR (DMSO-d6) δ 3.72 (8H, m, 4×CH2), 3.87 (3H, s, OMe), 4.01 (3H, s, OMe), 6.72 (2H, d, J=8.8 Hz, ArH), 7.07 (1H, dd, J=2.2 and 8.1 Hz, ArH), 7.41 (2H, d, J=8.8 Hz, 2×ArH), 7.47 (2H, m, 2×ArH), 7.65 (3H, m, ArH), 7.99 (2H, d, J=10.3 Hz, 2×ArH), 8.80 (1H, d, J=8.8 Hz, ArH), 9.25 (2H, brs, exchangeable, 2×NH). Anal. Calcd. for (C28H28Cl2N4O3): C, 62.61; H, 5.23; N, 10.39. Found: C, 62.34; H, 4.99; N, 10.59.

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