反应详情

2,4,5-Trifluorophenol (533 mg, 3.60 mmol), 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-pyrazinyloxy]ethanol (972 mg, 3.00 mmol), TMAD (619 mg, 3.60 mmol) and polymer-bound triphenylphosphine (Fluka) (1.2 g, 3.6 mmol) were shaken in dichloromethane (10 mL) under nitrogen for about 21 h. The polymer was filtered off and washed with dichloromethane. The solvent was evaporated and the residue was dissolved in CHCl3 and washed with 1 M Na2CO3 and brine. Removal of solvent in vacuo and purification of the residue by column chromatography on silica gel using CHCl3→CHCl3/MeOH (98:2) as eluent gave 791 mg (58%) of the title compound as its N-t-BOC derivative. The N-t-BOC intermediate (700 mg, 1.54 mmol) was treated with TFA/dichloromethane/H2O (42:53:5; 4 mL) and kept at room temperature for 50 min with stirring. The solution was concentrated and the residue precipitated with MeOH/ether. This material was dissolved in 50% aqueous MeOH and passed through an anion exchange resin (Dowex-1 X8, Cl−, 4 g) eluting with 50% aqueous MeOH. Evaporation of the solvent in vacuum gave the title compound. Yield: 513 mg (85%); mp 193-195° C.; MS-EI m/z 354 (M)+; HRMS m/z calcd for C16H17F3N4O2 (M)+ 354.1304, found 354.1301. Anal. (C16H17F3N4O2.HCl) C, H, N.

1. filtrationThe polymer was filtered off
2. washwashed with dichloromethane
3. customThe solvent was evaporated
4. dissolutionthe residue was dissolved in CHCl3
5. washwashed with 1 M Na2CO3 and brine
6. customRemoval of solvent
7. customin vacuo and purification of the residue by column chromatography on silica gel