Phosphorus pentachloride → HCID 59799756, compound

Participants

Reaction Steps

2-(4-Ethoxy-phenyl)-N-[2-(1-methyl-piperidin-4-ylamino)-5-nitro-phenyl]-acetamide 53 (190 mg, 0.461 mmol), Phosphorous pentachloride (100.7 mg, 0.483 mmol) were dissolved in anhydrous chloroform (10 mL) in a small, argon purged flask fitted with an condenser and magnetic stirbar. The solution was heated to reflux in an oil bath for 4 hours and cooled to room temperature overnight. The solid that had precipitated from the reaction mixture was collected on a sintered glass funnel and washed with a small amount of chloroform. The sticky solid was washed off the funnel in methanol and concentrated to residue. The residue was taken up in H2O and chloroform and 2M ammonium hydroxide solution added to adjust pH to 9-10. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with chloroform and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using silica gel column chromatography eluting with a solvent system of 5% 2M NH3 in methanol/95% dichloromethane to afford a pale yellow oil 54 2-(4-Ethoxy-benzyl)-1-(1-methyl-piperidin-4-yl)-5-nitro-1H-benzimidazole Yield: 127 mg (70.0%). 1H NMR (DMSO) δ: 1.29 (t, 3H, J=7.0), 1.39 (br d, 2H, J=9.8), 1.89-1.97 (m, 2H), 2.19 (s, 3H), 2.20-2.31 (m, 2H), 2.82 (br d, 2H, J=11.2), 3.96 (q, 2H, J=7.0), 4.29-4.37 (m, 1H), 4.37 (s, 2H), 6.87 (d, 2H, J=8.7), 7.17 (d, 2H, J=8.4), 7.82 (d, 1H, J=9.0), 8.07 (dd, 1H, J=9.0, 2.4), 8.48 (d, 1H, J=2.3); MS (ESI): 395 (MH+, 100%).

Provenance & Evidence