反应详情

To a solution of Intermediate 13b (1.15 g, 5.0 mmol), 2-(4-methyl-piperazin-1-yl)-ethanol (864 mg, 6.0 mmol), and triphenylphosphine (2.62 g, 10.0 mmol) in THF (10 mL), was added diisopropyl azodicarboxylate (2.0 g, 10.0 mmol) dropwise and stirred for 75 min. The mixture was diluted with diethyl ether (50 mL) and extracted with 10% aqueous citric acid soln (2×). The combined aqueous layers were basified with solid potassium carbonate until pH=9. The aqueous layer was then extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with brine, dried (NaSO4) and evaporated in vacuo. Purification by FCC using 0-12% [9:1 MeOH/880 ammonia] in DCM. The resulting product was crystallised (diethyl ether) to give the title compound (270 mg, 0.756 mmol, 15%). LCMS (Method 1): Rt 2.31, 1.72 min, m/z 358/359 [MH+].

1. extractionextracted with 10% aqueous citric acid soln (2×)
2. extractionThe aqueous layer was then extracted with ethyl acetate (3×)
3. washThe combined ethyl acetate layers were washed with brine
4. dry with materialdried (NaSO4)
5. customevaporated in vacuo
6. customPurification by FCC
7. customThe resulting product was crystallised (diethyl ether)