反应详情

温度

40 °C

A suspension of N-(2-aminoethyl)-2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzamide (50 mg, 101 μmol), chlorotrimethylsilane (39 μl, 304 μmol), sodium iodide (46 mg, 304 μmol), and TEA (42 μL, 304 μmol) in DCM (2 mL) was stirred for 3 hours at 40° C. in an appropriately sealed vial. The reaction was then partitioned between DCM (5 mL) and 1 M NaOH (2 mL). The organic layer was then separated and dried over MgSO4, concentrated onto dry silica (2 g) then purified on silica (4 g) by washing with 5% MeOH, then eluting product with 4->10% NH3 in MeOH (2M)/DCM. The product was isolated as a white solid. (ESI pos. ion) m/z: 476 (MH+); calc'd for C25H22ClN5O3: 475. 1H NMR (400 MHz, DMSO-d6) □ ppm 3.65 (s, 4 H) 3.87 (s, 3 H) 4.69 (dd, J=7.34, 3.42 Hz, 4 H) 6.95 (d, J=5.28 Hz, 1 H) 7.03 (dd, J=9.10, 2.45 Hz, 1 H) 7.12 (d, J=9.78 Hz, 1 H) 7.28 (d, J=2.35 Hz, 1 H) 7.67 (d, J=8.22 Hz, 1 H) 7.83-7.92 (m, 2 H) 7.97 (d, J=1.56 Hz, 1 H) 8.13 (d, J=9.78 Hz, 1H) 8.62 (d, J=5.28 Hz, 1 H).

1. customThe reaction was then partitioned between DCM (5 mL) and 1 M NaOH (2 mL)
2. customThe organic layer was then separated
3. dry with materialdried over MgSO4
4. concentrationconcentrated onto dry silica (2 g)
5. customthen purified on silica (4 g)
6. washby washing with 5% MeOH
7. customThe product was isolated as a white solid