反应详情

温度

40 °C

To a stirred solution of methyl 4-(4-(dibutylcarbamoyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (200 mg, 0.38 mmol) in DMF (8 mL) was added K2CO3 (107 mg, 0.77 mmol) and 3-bromopropanol (54 mg, 0.38 mmol). The reaction mixture was heated at 40° C. for 4 h, cooled to room temperature, diluted with MTBE, and quenched with water. The organic layer was separated and the aqueous layer was extracted with MTBE (3×). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to provide crude product. The crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes) to provide the title compound (67 mg, 32%). 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.19-8.15 (m, 1H), 8.04 (dd, J=11.2, 1.6 Hz, 1H), 7.62 (s, 0.5H), 7.55 (s, 0.5H), 7.50-7.46 (m, 1H), 7.25-7.14 (m, 3.5H), 6.94 (d, J=7.2 Hz, 0.5H), 4.84-4.59 (m, 2H), 4.29-4.13 (m, 2H), 3.96 (s, 3H), 3.82-3.70 (m, 2H), 3.50-3.35 (m, 4H), 3.31-2.88 (m, 4H), 1.89-1.87 (m, 2H), 1.55-1.49 (m, 2H), 1.40-1.05 (m, 6H), 0.93-0.88 (m, 3H), 0.74 (t, J=7.2 Hz, 1.5H), 0.65 (t, J=7.2 Hz, 1.5H); MS(ESI+) m/z 575.6 (M+H)+.

1. temperaturecooled to room temperature
2. customquenched with water
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with MTBE (3×)
5. dry with materialThe combined organic layer was dried over Na2SO4
6. concentrationconcentrated in vacuo
7. customto provide crude product
8. customThe crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes)