反应详情

温度

100 °C

A vial was charged with (3R,3aR,6R,6aR)-6-[5-(4-bromophenyl)-6-chloro-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (501.8 mg, 0.861 mmol), tert-butyl 4,6-dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylate (240.3 mg, 1.148 mmol), tripotassium phosphate (581.6 mg, 2.74 mmol), and copper (I) iodide (37.2 mg, 0.195 mmol). The vial was evacuated (3×) and backfilled with nitrogen. Trans-N,N′-dimethylcyclohexane-1,2-diamine (55 μl, 0.348 mmol) and dioxane (1.7 ml) were added to the vial to give a hazy suspension that was heated to 100° C. for 24 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (100 ml) and water (100 ml). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×30 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a pale green residue. Flash chromatography of the residue utilizing a 40 g silica RediSep Rf® column and employing a 0-100% EtOAc/hexane gradient afforded a mixture of the two pyrazole linked regioisomers as a pale amber foam. LC-MS: calculated for C34H43ClN6O7Si 710.27 observed m/e: 711.29 (M+H)+ (Rt 1.30/2 min)

1. customThe vial was evacuated (3×)
2. customto give a hazy suspension that
3. temperatureThe reaction mixture was cooled to room temperature
4. custompartitioned between EtOAc (100 ml) and water (100 ml)
5. extractionThe aqueous layer was extracted with EtOAc (2×50 ml)
6. washwashed with brine (1×30 ml)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated under reduced pressure
10. customto give a pale green residue
11. customgradient afforded
12. custom2 min