反应详情

温度

42.5 °C

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.

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. stirringAfter being stirred at room temperature for 3 h
6. customevaporated in vacuo to dryness
7. dissolutionThe residue was dissolved in a mixture of CHCl3/MeOH
8. additionmixed silica gel (10 g)
9. customevaporated in vacuo to dryness
10. customchromatographed
11. additionThe fractions containing the main product
12. customevaporated in vacuo to dryness
13. customthe residue was recrystallized from acetone