反应详情

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). The filtrate containing crude N-mustard isocyanate 19 was evaporated in vacuo to dryness and the residue was dissolved in dry DMF (5 mL) and then added dropwise into the solution of N-acridin-9-yl-5-methylbenzene-1,3-diamine (0.517 g, 1.7 mmol) in dry DMF (25 mL) containing pyridine (2 mL) at −10° C. The reaction mixture was allowed to cool down to room temperature and continuously stirred for 24 h and then evaporated in vacuo to dryness. The residue was dissolved in a mixture of CHCl3/MeOH containing silica gel (10 g) and evaporated under reduced pressure to dryness. The residue was put on the top of a silica gel column (4×30 cm) and chromatographed by using CHCl3/MeOH (100:3 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness to give 1-[3-(acridin-9-ylamino)-5-methylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea (BO-1079), 0.375 g (39%); mp 280-285° C.; 1H NMR (DMSO-d6) δ 2.26 (3H, s, Me), 3.68 (8H, s, 4×CH2), 6.68 (2H, d, J=9.0 Hz, ArH) 6.75-6.89 (1H, m, ArH), 7.19-7.32 (3H, m, ArH), 7.40-7.62 (3H, m, ArH), 7.93-8.14 (4H, m, ArH), 8.29 (2H, d, J=9.0 Hz, ArH), 8.94 (1H, brs, exchangeable, NH), 9.37 (1H, brs, exchangeable, NH), 11.51 (1H, brs, exchangeable, NH). Anal. Calcld. for (C31H29C12N5.0.3; H2O): C, 60.88; H, 6.11; N, 11.45. Found: C, 61.08; H, 6.18; N, 11.32.

1. customThe reaction mixture was evaporated
2. additionthe residue diluted with THF (20 mL)
3. filtrationfiltered through a pad of Celite
4. washwashed with THF (5 mL)
5. additionThe filtrate containing crude N-mustard isocyanate 19
6. customwas evaporated in vacuo to dryness
7. dissolutionthe residue was dissolved in dry DMF (5 mL)
8. stirringcontinuously stirred for 24 h
9. customevaporated in vacuo to dryness
10. dissolutionThe residue was dissolved in a mixture of CHCl3/MeOH
11. additioncontaining silica gel (10 g)
12. customevaporated under reduced pressure to dryness
13. customchromatographed
14. additionThe fractions containing the main product
15. customevaporated in vacuo to dryness