反应详情

温度

50 °C

To a suspension of 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonic acid (250 mg, 0.43 mmol) in DCM (5 mL) was added thionyl chloride (1 mL) and DMF (10 uL, anhyd). The reaction mixture was heated 2 h at 50° C., concentrated, diluted with DCM, and concentrated to dryness. The sulfonyl chloride intermediate was diluted with DCM (3 mL) and added slowly to a well-stirred mixture of 3-(2-aminoethyl)-1-methylpyridinium chloride hydrochloride (100 mg, 0.58 mmol) and K2CO3(178 mg, 1.29 mmol) in CH3CN (10 mL). After stirring 2 h, the reaction mixture was filtered and concentrated. The residue was purified by chromatography (10-20% MeOH/DCM) to afford the title compound as a solid (18 mg, 6%). 1H NMR (400 MHz, CDCl3) δ 9.13 (s, 1H), 8.77 (s, 1H), 8.40-8.32 (m, 1H), 8.03 (s, 1H), 7.71 (s, 1H), 7.51 (d, J=8.29 Hz, 1H), 7.15 (s, 1H), 6.96-6.78 (m, 3H), 6.62-6.38 (m, 5H), 4.54 (s, 3H), 4.03 (s, 2H), 3.77 (s, 4H), 3.52-3.41 (m, 4H), 3.22-3.12 (m, 2H), 1.82-1.58 (m, 6H), 1.50 (s, 7H), 1.21 (t, J=7.02 Hz, 4H); MS (EI) m/z 701 [M]+.

1. concentrationconcentrated
2. additiondiluted with DCM
3. concentrationconcentrated to dryness
4. additionThe sulfonyl chloride intermediate was diluted with DCM (3 mL)
5. filtrationthe reaction mixture was filtered
6. concentrationconcentrated
7. customThe residue was purified by chromatography (10-20% MeOH/DCM)