Pyridine → HCID 131719067, compound

Participants

Reaction Steps

4-[3-[4-(Diphenylmethyl)-1-piperazinyl]propoxy]indole-2-carboxamide (EXAMPLE 5, 1.45 g) and pyridine (1.18 ml) in dioxane (442) ml) is cooled to 12°. Trifluoroacetic anhydride (1.1 ml) in dioxane (8 ml) is added dropwise over 15 min (the reaction temperature remained between 12° and 14° ). The mixture is stirred for 2 hr at 20°-25°, diluted with methylene chloride and the mixture is washed with aqueous sodium bicarbonate, water and finally saline. The organic solution is dried over magnesium sulfate and concentrated to give a solid. The residue is dissolved in ether, filtered through magnesol, and the solution concentrated to give the free base of the title compound. The hydrochloride salt is prepared and recrystallized with an impurity. The solids and filtrates are combined, concentrated, and the residue partitioned between saturated sodium bicarbonate and methylene chloride to give the free base. This is chromatographed over silica gel (500 ml), eluting with methanol/methylene chloride (2.5/97.5). Twenty ml fractions are collected. Fractions 58-84 contained clean product. The hydrochloride salt is prepared from an ether solution by the addition of ethereal hydrochloric acid. Recrystallization from methanol/acetone/ether gives the title compound, mp 231°-2°. The proposed structure is supported by NMR, IR and mass spectra.

Provenance & Evidence