[Synthesis]
Step 4. A mixture of 1,9-dihydro-4H-pyrimido[4,5-b]indol-4-one (7.0 g, 37.8 mmol) was heated to reflux for 2 hours with phosphorus oxychloride (8.69 g, 56.7 mmol) and N,N-diisopropylethylamine (7.33 g, 56.7 mmol) in acetonitrile (151 mL). After completion of the reaction, the mixture was cooled to room temperature and diluted with 50 mL of methanol. Insoluble solids were removed by filtration and the filter cake was washed with about 250 mL of methanol. Subsequently, the filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography (ISCO, 120 g silica gel column, 0-50% ethyl acetate/dichloromethane gradient elution). The gelatinous solid obtained after purification was ground with ethyl acetate, the solid was collected by filtration and dried to give 4-chloro-9H-pyrimido[4,5-b]indole (1.95 g, 25% yield) as a yellow powder. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 12.79 (br.s., 1H), 8.79 (s, 1H), 8.30 (d, J = 7.81 Hz, 1H), 7.60-7.68 (m, 2H), 7.44 (s, 1H); mass spectrum (m/z) 204.0 (M + H)+. |