Triethylamine → 1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-(2-methylquinolin-4-yl)urea

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.612 g, 2.0 mmol) in dry CHCl3 (35 mL) containing Et3N (0.4 mL) was added dropwise a solution of triphosgene (231 mg, 0.8 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). The filtrate and washings were combined and then added dropwise into a solution of commercially available 4-amino-2-methylquinoline (0.177 g, 2.0 mmol) in dry DMF (15 mL) containing Et3N (0.5 mL) at 0° C. After being stirred at room temperature for 3 h, the reaction mixture was heated at 40-45° C. for 16 h and then evaporated in vacuo to dryness. The residue was dissolved in a mixture of CHCl3/MeOH, mixed silica gel (10 g) and then evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (2×30 cm) and chromatographed using CHCl3/MeOH (100:2 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness and the residue was recrystallized from acetone to give 1-{4-[bis(2-chloroethyl)amino]phenyl}-3-(2-methylquinolin-4-yl)urea (BO-1038); 187 mg (40.1%); mp 128-129° C.; 1H NMR (CHCl3-d6) δ 2.63 (3H, s, Me), 3.57 (4H, t, J=6.6 Hz, 2×CH2), 3.66 (4H t, J=6.6 Hz, 2×CH2), 6.56 (2H, d, J=7.9 Hz, 2×ArH), 7.12-7.14 (1H, m, ArH), 7.21 (2H, d, J=8.8 Hz, 2×ArH), 7.26 (1H, s, ArH), 7.44-7.56 (2H, m, 2×ArH), 7.92 (2H, d, J=8.5 Hz, 2×ArH), 8.14 (1H, s, ArH), 8.40 (1H, brs, exchangeable, NH). Anal. Calcd. for (C21H22Cl2N4O: C, 57.94; H, 5.56; N, 12.87. Found: C, 58.27; H, 5.56; N, 12.6.

Herkunft & Nachweise