2-Chloroethyl isocyanate → 3-(2-chloroethyl)-1-methyl-2,4(1H,3H)-quinazolinedione
Reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](OCC)=[O:10].[Cl:14][CH2:15][CH2:16][N:17]=[C:18]=[O:19]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:3]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:9](=[O:10])[N:17]([CH2:16][CH2:15][Cl:14])[C:18]1=[O:19]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
N-Methyl-2-carboethoxyaniline (5.0 g, 28 mmol) was treated with 2-chloroethylisocyanate (2.86 mL, 28 mmol) at reflux in toluene for 18 hours. The reaction was cooled to 25° C., and the crystalline product was collected by filtration to yield the intermediate 1-methyl-3-(2-chloroethyl)-quinazoline-2-4-dione. The intermediate quinazolinedione (0.53 g, 2.2 mmol) and cis-6-methoxy-2,3,3a,4,5,9b-[1H]-benz[e]isoindole (0.38 g, 1.87 mmol) were combined in acetonitrile (3 mL) and diisopropylethylamine (0.8 mL) was added. The reaction mixture was heated at reflux for 18 hours. The resulting product was converted to its HCl salt and recrystallized from acetone:ether to yield the title compound (0.30 g, 40%) as a white solid. m.p. 215°-217° C. (dec). 1H NMR (300 MHz, CDCl3) of the free base δ 8.2 (dd, 1H), 7.7 (dt, 1H), 7.1- 7.32 (m, 3H), 6.75 (t, 2H), 4.48 (m, 3H), 4.1-4.3 (m, 2H), 3.81 (s, 3H), 3.68 (m, 1H), 3.6 (s, 3H), 3.35-3.5 (m, 2H), 2.87-4.3 (m, 2H), 2.72-2.87 (m, 2H), 2.52-2.65 (m, 1H), 1.88-2.0 (m, 1H), 1.55-1.7 (m, 1H). MS (DCI/NH3) m/e 406 (M+H)+. Anal calcd for C24H27N3O3.HCl. H2O: C, 62.67; H, 6.57; N, 9.14. Found: C, 62.52; H, 6.51; N, 9.03.