反应详情

To a solution of 1-(2-iodophenyl)-N-methyl-3-isoquinolinecarboxamide (22 mg, 0.06 mmol) in DMF (2 mL) was added 60% NaH (12 mg, 0.30 mmol) in one portion. The mixture was stirred under Ar at room temperature for 40 min. Then, 3-fluoropropyl bromide (22 ul, 0.30 mmol) was added. After stirring under Ar at room temperature for 24 h, the mixture was quenched by adding H2O (7 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried (MgSO4), filtered. The filtrate was concentrated in vacuo. The residue was chromatographed (SiO2, 30% ethyl acetate/hexane, 0.035% Et3N), thereby affording a semisolid (6 mg, 23%), and starting material (17.7 mg). 1H NMR (CDCl3) d 1.96-2.22 (m, 2 H, CH2), 3.16, 3.20 (two s, total 3 H, N-methyl), 3.59-3.85 (m, 2 H, N--CH2), 4.47 (qt, J=79.8, 47.1, 6 Hz, 2 H, CH2F), 7.21 (dt, J=7.5, 0.9 Hz, 1 H, aromatic), 7.36 (dd, J=7.5, 1.5 Hz, 1 H, aromatic), 7.51 (t, J=7.2 Hz, 1 H, aromatic), 7.56 (d, J=3.9 Hz, 2 H, aromatic), 7.69-7.81 (m, 1 H, aromatic), 7.99 (t, J=7.8 Hz, 1 H, aromatic), 8.11, 8.18 (two s, total 1 H, aromatic). HRMS calcd. for C20H18FIN2O: 448.0448. Found: 448.0456.

1. stirringAfter stirring under Ar at room temperature for 24 h
2. customthe mixture was quenched
3. additionby adding H2O (7 mL)
4. extractionThe mixture was extracted with CH2Cl2 (3×15 mL)
5. dry with materialThe combined organic layers were dried (MgSO4)
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customThe residue was chromatographed (SiO2, 30% ethyl acetate/hexane, 0.035% Et3N)