Sodium hydride → 3-(4-Chlorophenylmethyl)-5-(4-(4-methylpiperazin-1-yl)-1H-indol-2-yl)-1,2,4-oxadiazole

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Reaction Steps

To a stirred solution of (4-chlorophenyl)acetamidoxime (2.21 g from above, assumed 10 mmol, 15 equivalents) and sodium hydride (60% in oil, 0.460 g, 11.5 mmol, 17 equivalents) in anhydrous tetrahydrofuran (25 mL) was added crude 4-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol4-yl)piperazine (0.225 g from above, assumed 0.68 mmol), and the resulting reaction mixture was heated at reflux under nitrogen for 6 hours. A saturated solution of sodium hydrogen carbonate (25 mL) was added, and the resulting aqueous mixture was extracted with ethyl acetate (2×25 mL). The organic extracts were combined, dried (magnesium sulfate), and evaporated under reduced pressure. The residue was chromatographed using silica gel (approximately 25 g) and elution with methylene chloride/methanol/ammonium hydroxide [10:1:0.1] to afford the title compound (0.013 g, 0.03 mmol, 4%) as an off-white foam: 13C NMR (acetone-d6) δ170.3, 169.5, 147.2, 139.7, 135.0, 132.3, 130.7, 128.5, 126.2, 121.5, 119.9, 107.0, 106.4, 106.2, 55.3, 51.2, 45.5, 31.0; LRMS (m/z, relative intensity) 409 ([M+ with 37Cl], 30), 408 (27), 407 ([M+ with 35Cl], 100), 392 (7), 337 (23), 322 (16), 170 (16), 70 (41); HRMS calculated for C22H22ClN5O [with 35Cl] 407.1516, found 407.1516.

Provenance & Evidence