Tetrahydrofuran → 6-Chloro-2-[[4-(2-pyrimidinyl)-1-piperazinyl]methyl]imidazo[1,2-a]pyridine

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (Example 4, Step 1; 0.335 g), 1-(pyrimidin-2-yl)piperazine dihydrochloride (Aldrich; 0.395 g), triethylamine (Aldrich; 0.522 g), THF (5 mL), and dichloromethane (5 mL) is heated at 80° C. for 45 min and then at 60° C. for 5 h, at which time DMF (1 mL) is added. After stirring for a total of 10.5 h, the mixture is allowed to cool and stir at room temperature for an additional 12 h. The solvents are then removed under reduced pressure and the residue is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate and concentrated. The residue is chromatographed on silica gel using methanol/dichloromethane (4/96) and the appropriate fractions are combined and concentrated to give 0.228 g of the title compound. Crystallization from methanol-dichloromethane-hexane gives 0.315 g of the title compound in two crops; mp 114-115° C.; MS m/z 328, 330; IR (mineral oil) 1481, 1357, 1584, 1439, 1253, 1548 cm-1. 1H NMR (CDCl3) δ2.64, 3.76, 3.87, 6.48, 7.12, 7.52, 7.54, 8.14, 8.30.

Provenance & Evidence