(Diethylamino)sulfur trifluoride → N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-(2-fluoroethoxy)ethoxy)-5-methylbenzamide

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Reaction Steps

To solution of compound 5a (0.20 g, 0.41 mmol) in dichloromethane (60 ml) was added slowly (Diethylamino)sulfur trifluoride (DAST) (0.13 g, 0.81 mmol) at 0° C. The reaction mixture was stirred overnight under an atmosphere of nitrogen and then quenched with water (30 ml). The organic layer was separated and washed with saturated sodium carbonate solution (2×15 ml) and dried over sodium sulfate. Volatile components were removed under reduced pressure. The crude product was purified by silica gel column chromatography using ether:methanol (100:20) as the mobile phase to give 6a (0.07 g; 36% yield) as a viscous colorless oil. 1H NMR spectrum (300 MHz, CDCl3): 1.65-1.69 (m, 4H), 2.32 (s, 3H), 2.50-2.59 (m, 2H), 2.70-2.73 (m, 2H), 2.78-2.82 (m, 2H), 3.45-3.48 (m, 2H), 3.54 (s, 2H), 3.69-3.73 (m, 1H), 3.72-3.82 (m, 7H), 3.87-3.90 (m, 2H), 4.19-4.22 (m, 2H), 4.43-4.47 (m, 1H), 4.59-4.63 (m, 1H), 6.50 (s, 1H), 6.58 (s, 1H), 6.80-6.84 (d, 1H), 7.05-7.20 (m, 1H), 7.97-7.99 (m, 1H), 8.21 (s, 1H). The free base was converted into oxalic acid salt and re-crystallized in methanol and ethyl acetate solvent. Mp 89.2-89.55° C. Elemental Analysis: C27H37FN2O5.H2C2O4.0.5H2O (C, H, N). Calcd: C, 59.27; H, 6.86; N, 4.77; Found: C, 58.95; H, 6.84; N, 4.85.

Provenance & Evidence