2-Chloroethyl isocyanate → 3-(2-chloroethyl)-1-methyl-2,4(1H,3H)-quinazolinedione

HRID 440879Notes

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

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.

Workup

filtrationthe crystalline product was collected by filtration

Sources & evidence

ORD record: ord-86a9c8aa552845e3804a9e74cba0e051
Source dataset: uspto-grants-1996_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05521181

Reaction notes

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