Benzyl Alcohol → HCID 21219108, compound

Participants

Reaction Steps

Rapidly add trichloromethylchloroformate (0.16 mL, 1.32 mmol) to a stirred suspension of 8-(p-aminobenzenesulfonamido)-6-(3-methyl-2-pyridinyl)-1,7-naphthyridine (0.43 g, 1.10 mmol), triethylamine (0.183 mL, 1.32 mmol) and 4-dimethylaminopyridine (0.03 g) in dichloromethane (25 mL) at 25° C. Stir for 1 hour at room temperature. Add this reaction mixture to a stirred solution of the lithium salt of benzyl alcohol [prepared by stirring a 1M solution (1.5 mL, 1.5 mmol) of lithium bis(trimethylsilyl)amide in tetrahydrofuran with benzyl alcohol (0.15 mL, 1.45 mmol) in dichloromethane (20 mL) for 0.5 hour]. Stir the resultant mixture for 3 days at room temperature. Introduce additional lithium salt of benzyl alcohol [prepared as described above from a 1M solution (3 mL, 3 mmol) of lithium bis(trimethylsilyl)amide in tetrahydrofuran with benzyl alcohol (0.30 mL, 2.90 mmol) in dichloromethane (1 mL)] and reflux for 24 hours. Remove solvent under reduced pressure, and flash chromatograph on a column of silica gel, eluting with a stepped gradient of dichloromethane-methanol-ammonium hydroxide (95:5:0.1→90:9:0.1) to obtain the title compounds I and II. Reflux the less polar solid thus isolated in methanol-ethanol (1:1) for 5-10 minutes, cool to room temperature, and filter to obtain title compound I as a 0.25 hydrate, C28H23N5O4S.0.25 H2O, mp 229.5-231° C. (dec). FABMS: MH+ 526 (100%). Crystallize from ethanol (5 mL) the more polar solid eluted from the column to obtain title compound II as a 0.5 hydrate, C21H18N6O3S.0.5 H2O, mp 258.5-260° C. (dec). FABMS: MH+ 435 (94%).

Provenance & Evidence