反应详情

A solution of 197.HCl (81 mg, 0.25 mmol) in couc. H2SO4 (9 mL) and water (1 mL) was heated at. 60° C. for 1 h, then poured into cold water. Conc. aqueous NH3 was carefully added until the pH of the mixture was 3, followed by careful addition of solid KHCO3 until the pH of the mixture was 8. The mixture was extracted with cold CH2Cl2 (×3), and the combined organic extracts were washed with water, brine and dried. The solvent was evaporated and the residue was dissolved in CH2Cl2MeOH. The solvents were concentrated until precipitation began. The precipitate was filtered off and washed with MeOH to give crude 1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-8-carboxamide (198) (37 mg, 48%) as red crystals: mp>300° C.; 1H NMR [(CD3)2SO] δ (two H not observed) 8.32 (d, J=1.3 Hz, 1H), 8.17 (d, J=9.1 Hz, 1H), 7.80 (dd, J=9.1, 1.7 Hz, 1H), 7.72 (s, 1H), 7.53 (br s, 1H), 4.26-4.18 (m, 1H), 3.99 (dd, J=10.9, 3.8 Hz, 1H), 3.83 (t, J=10.1 Hz, 1H), 3.77-3.69 (m, 2H). 1H NMR also showed the presence of an unidentified impurity (ca. 10%) which was not removed by chromatography. HRMS (CI) calcd. for C14H1235ClN3O3 (M+) m/z 305.0567, found 305.0564.

1. extractionThe mixture was extracted with cold CH2Cl2 (×3)
2. washthe combined organic extracts were washed with water, brine
3. customdried
4. customThe solvent was evaporated
5. dissolutionthe residue was dissolved in CH2Cl2MeOH
6. concentrationThe solvents were concentrated until precipitation
7. filtrationThe precipitate was filtered off
8. washwashed with MeOH