Triethylamine → p-[(N,N-bis(2-chloroethyl)amino)]phenylcarbamoyl chloride hydrochloride

関与物質

反応手順

A solution of diphosgene (197 mg, 1.2 mmol.) in dry CH3Cl was added dropwise to a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (37) (0.306 g, 1.0 mmol) in dry THF (25 mL) containing Et3N (0.5 mL) in an ice bath with vigorous stirring for 30 min. It formed crude p-[(N,N-bis(2-chloroethyl)amino)]phenylcarbamoyl chloride hydrochloride (38). The reaction mixture was filtered through a pad of Celite and washed with THF (5 mL). The filtrate and washings were combined and was then added dropwise into a solution of 3-amino-5-(4-methylacridin-9-ylamino)phenyl]-methanol18 (0.329 mg, 1.0 mmol) in dry DMF (20 mL) containing Et3N (0.5 mL) at 0° C. and stirred at room temperature for 16 h. The solvent was removed by distillation under reduced pressure to dryness and the residue was dissolved in CHCl3/MeOH and mixed with silica gel (5 g) and then evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (2×20 cm) and chromatographed using CHCl3/MeOH (100:2 v/v) as eluent. The fractions containing the main product were combined and concentrated in vacuo and the residue was recrystallized from CHCl3/MeOH to give 1-{4-[bis(2-chloroethyl)amino]phenyl}-3-[3-hydroxymethyl-5-(4-methylacridin-9-ylamino)phenyl]urea (16, BO-1050), 179 mg (30%); mp 251-252° C.; 1H NMR (DMSO-d6) δ 3.64-3.71 (8H, m, 4×CH2), 4.00 (3H, s, Me), 4.47 (2H, d, J=5.1 Hz, CH2) 5.11 (1H, t, J=5.1 Hz, exchangeable, OH), 6.35 (1H, s, ArH), 6.68 (2H, d, J=8.8 Hz, 2×ArH) 6.75 (1H, s, ArH), 6.88-7.18 (4H, m, 4×Ar H), 7.24 (2H, d, J=8.8 Hz, 2×ArH) 7.52 (2H, s, 2×ArH), 7.83 (2H, s, 2×Ar H), 8.25 (1H, s, ArH) 8.40 (1H, s, ArH), 10.24 (1H, s, exchangeable, NH). Anal. Calcld. for (C32H31Cl2N5O2.3H2O): C, 59.81; H, 5.80; N, 10.89. Found: C, 59.74; H, 5.79; N, 9.67.

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