反应详情

3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine (0.795 g, 3.10 mmol) was dissolved in N,N-Dimethylformamide (12.0 mL) and N,N-Diisopropylethylamine (1.50 mL, 8.61 mmol). Potassium carbonate (1.28 g, 9.30 mmol) was added, followed by 3-Chloropropane-1-sulfonyl chloride (0.450 mL, 3.70 mmol) and stirred overnight. After 24 h, a second aliquot of N,N-Diisopropylethylamine (2.00 mL, 11.5 mmol) and 3-Chloropropane-1-sulfonyl chloride (0.50 mL, 4.1 mmol) was added and stirred additionally. When conversion had reached ca. 90%, the mixture was treated with water (40 mL) and EtOAc (40 mL). The layers were separated, the aq. extr. with EtOAc (3×20 mL) and the comb. org. diluted with hexane (20 mL) and washed with water (30 ml) and brine (30 mL). After drying over sodium sulfate, the mixture was filtered and conc. in vacuo and applied to a 25 g ISCO loading cartridge. Purification on ISCO (40 g column, 10-70% EtOAc:Hex) afforded 7-[3-(1,1-Dioxido-1,2-thiazolidin-2-yl)phenyl]-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine (0.52 g; Yield=46%) as a yellow solid. 1H-NMR (CDCl3): 8.74 (s, 1H), 8.06 (s, 1H), 7.86 (d, 1H, J=7.9 Hz), 7.47 (m, 1H), 7.28 (m, 1H), 7.27 (s, 1H), 7.12 (d, 1H, J=4.8 Hz), 6.89 (d, 1H, J=4.8 Hz), 3.86 (t, 2H, J=6.5 Hz), 3.42 (t, 2H, J=7.4 Hz), 2.62 (s, 3H), 2.58 (m, 2H).

1. waitAfter 24 h
2. stirringstirred additionally
3. customThe layers were separated
4. additiondiluted with hexane (20 mL)
5. washwashed with water (30 ml) and brine (30 mL)
6. dry with materialAfter drying over sodium sulfate
7. filtrationthe mixture was filtered and conc. in vacuo
8. customPurification on ISCO (40 g column, 10-70% EtOAc:Hex)