反应详情

温度

0 °C

4-CBZ-piperidylzinc iodide (generated from of 4-CBZ-piperidyl iodide (345 mg, 1.0 mmol) using zinc metal and dibromoethane) (0.8 mmol) was added at 50° C. to a solution of 8,5-dichloro-5H-dibenzo[b,e][1,4]diazepine (160FE64) (106 mg, 0.4 mmol) and PdCl2(PPh3)2 (18 mg, 0.04 mmol) in dry THF (2 ml). The reaction was shaken for 16 h and then quenched by the addition of aqueous saturated NH4Cl-solution. The resulting mixture was extracted twice with ether and the combined ethereal phases were washed with brine and dried (Na2SO4). Filtration followed by concentration at reduced pressure of the organic phase gave a crude product. BBr3 (100 μl) added at −30° C. was added to the crude product dissolved in CH2Cl2 (1 ml). The reaction temperature was then slowly increased to 0° C. TLC indicated complete conversion of the starting material and Et3N, H2O and EtOAc were sequentially added to the reaction mixture. The organic phase was washed with brine and dried (Na2SO4). Filtration followed by concentration at reduced pressure gave a crude product, which was purified by HPLC to give 2.3 mg of the title compound (160FE67A). MS (ESI) 312 (MH+). Purity for MH+ (UV/MS) 99/96.

1. customquenched by the addition of aqueous saturated NH4Cl-solution
2. extractionThe resulting mixture was extracted twice with ether
3. washthe combined ethereal phases were washed with brine
4. dry with materialdried (Na2SO4)
5. filtrationFiltration
6. concentrationfollowed by concentration at reduced pressure of the organic phase
7. customgave a crude product
8. additionwere sequentially added to the reaction mixture
9. washThe organic phase was washed with brine
10. dry with materialdried (Na2SO4)
11. filtrationFiltration
12. concentrationfollowed by concentration at reduced pressure
13. customgave a crude product, which
14. customwas purified by HPLC