2-Methoxyethanol → N-(2-chloro-5-(4-(2-methoxyethoxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide

Participants

Reaction Steps

(Some starting materials may be obtained from Aldrich, St. Louis, Mo.) To a solution of 2-methoxyethanol (0.2 mL, 2 mmol) in DMF (10 mL) at 0° C. was added sodium hydride, 60% dispersion in mineral oil (0.09 mL, 2 mmol). After the addition, the ice bath was removed. The reaction mixture was warmed up to rt and continued to stir at rt. After 20 min, N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.1 g, 0.2 mmol) was added. It was continued to stir for 20 h. LC/MS showed total conversion. Reaction was quenched with water. The resulting mixture was partitioned between EtOAc/water. The organic layer was washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified using SiO2 (12 g) chromatography with hexanes:acetone=80%:20% as the solvent system to afford the desired product as light yellow solid (25 mg). A peak at 28 min was collected. The solvent was removed in vacuo to afford the desired product as light yellow solid (80.0 mg). MS (ESI pos. ion) m/z: calc'd for C23H19ClFN3O4S: 487.1; found: 488.4 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.53 (s, 3 H) 3.90-4.00 (m, 2 H) 4.35-4.49 (m, 2 H) 6.84 (d, J=5.26 Hz, 1 H) 7.19 (t, J=8.55 Hz, 2 H) 7.88 (ddd, J=8.62, 4.17, 3.87 Hz, 3 H) 8.17 (d, J=8.77 Hz, 1 H) 8.33 (d, J=2.34 Hz, 1 H) 8.43 (d, J=1.90 Hz, 1 H) 8.50 (d, J=2.34 Hz, 1 H) 8.81 (d, J=5.26 Hz, 1 H).

Provenance & Evidence