反应详情

温度

92.5 °C

To a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (37) (0.918 g, 3 mmol) and charcoal (20 mg) in dry dioxane (30 mL) was added diphosgene (0.494 g, 2.5 mmol). The reaction mixture was heated at 90-95° C. for 5 h. After cooling, the reaction mixture was filtered through a pad of Celite and the filtrate containing crude mustard isocyanate 39 was added dropwise into the solution of 9-(5-amino-2-methyl-phenylamino)-5-methylacridine-4-carboxylic acid (2-dimethylaminoethyl)amide (0.732 g, 1.7 mmol)33 in dry DMF (25 mL) containing pyridine (2 mL) at −10° C. and then stirred at room temperature for 24 h. The solvent removed under reduced pressure to dryness and the residue was dissolved in a mixture of CHCl3/MeOH containing silica gel (10 gm) and evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (4×30 cm) and chromatographed using CHCl3/MeOH (100:5 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness. The residue was recrystallized from EtOH/hexane to give 9-[5-(3-{4-[bis(2-chloroethyl)amino]phenyl}ureido)-2-methyl-phenylamino]-5-methyl-acridine-4-carboxylic acid (2-dimethylaminoethyl)amide (19, BO-1053); 0.385 g (32%); mp 286-289° C.; 1H NMR (DMSO-d6) δ 2.19 (3H, s, Me), 2.67 (6H, m, NMe2), 2.85 (3H, s, Me), 3.14 (2H, brs, CH2), 3.63-3.69 (8H, m, 4×CH2), 3.85 (2H, brs, CH2), 6.41 (1H, m, ArH,), 6.65 (2H, d, J=9.0 Hz, ArH), 6.97 (1H, m, ArH), 7.24 (2H, d, J=9.0 Hz, ArH), 7.36-7.44 (1H, m, ArH), 7.51 (1H, m, ArH), 7.74 (2H, m, ArH), 7.93 (1H, m, ArH), 8.09 (1H, m, ArH), 8.41 (1H, m, ArH), 8.67 (1H, m, ArH), 9.04 (1H, brs, exchangeable, NH), 9.45 (1H, brs, exchangeable, NH), 12.18 (1H, brs, exchangeable, NH). Anal. Calcld. for (C37H41Cl2N7O2.6H2O): C, 54.91; H, 5.20; N, 12.34. Found: C, 55.08; H, 5.32; N, 12.44.

1. temperatureAfter cooling
2. filtrationthe reaction mixture was filtered through a pad of Celite
3. additionthe filtrate containing crude mustard isocyanate 39
4. customThe solvent removed under reduced pressure to dryness
5. dissolutionthe residue was dissolved in a mixture of CHCl3/MeOH
6. additioncontaining silica gel (10 gm)
7. customevaporated in vacuo to dryness
8. customchromatographed
9. additionThe fractions containing the main product
10. customevaporated in vacuo to dryness
11. customThe residue was recrystallized from EtOH/hexane