Iodine → HCID 58382134, compound

Participants

Reaction Steps

2-Bromo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (15.5 g, 43.0 mmol, prepared using A from Preparation #4 with ethynyltrimethylsilane, Q, A with 3,5-dibromopyrazin-2-amine, and B) in DMF (200 mL) was stirred for about 15 min at rt. The mixture was treated with powdered KOH (2.90 g, 51.6 mmol), then iodine (11.3 g, 44.4 mmol) was added in two roughly equal portions over about 15 min then the mixture was stirred for about 2 h at rt. To the mixture was added 60 wt % NaH (2.07 g, 51.6 mmol) in two roughly equal portions then stirred for about 10 min at rt. The mixture was cooled to about 0° C. then SEMCl (8.01 mL, 45.2 mmol) was added over about 10 min. After stirring for about 10 min at about 0° C. the mixture was allowed to warm to rt. After about 1 h the mixture was concentrated under reduced pressure then partitioned between EtOAc (300 mL) and water (200 mL). The organic layer was washed with saturated aqueous NaCl (100 mL) then the combined aqueous layers were extracted with EtOAc (100 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified on two successive 120 g silica columns with 8:2 heptane/EtOAc as an eluent to give 2-bromo-7-iodo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (20.1 g, 76%): LC/MS (Table 2, Method g) Rt=1.76 min; MS m/z 616 (M+H)+.

Provenance & Evidence