Dichloromethane → HCID 70078123, compound

Participants

Reaction Steps

A suspension of 0.49 g (1.5 mmol) of 3-(5-aminomethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one in 8 ml of methylene chloride was treated under argon with 0.77 ml (4.5 mmol) of N-ethyldiisopropylamine and 0.475 g (1.8 mmol) of α,α'-dibromo-o-xylene and stirred at room temperature under argon for 7 hrs. The solution was washed once with 10 ml of water, dried with sodium sulfate, filtered and evaporated. The crude product was purified by chromatography on 40 g of silica gel (methylene chloride/acetone 4:1, then 22:1), whereupon the eluate was evaporated and the residue was taken up in 3 ml of methanol. The solution was acidified with ethereal hydrochloric acid and the solvent was removed in a vacuum. The residue was dissolved in 3 ml of methanol, whereupon the solution was cooled to about 0° and diluted dropwise with 3 ml of ether. Thereby, white crystals separated slowly and were filtered off. There were obtained 190 mg (26%) of 8-fluoro-3-(5-isoindolin-2-ylmethyl-1,2,4-oxadiazol-3-yl)-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one hydrochloride (22:3) of m.p. 177°-184° (dec.).

Provenance & Evidence