Acetic Acid → HCID 58382188, compound

Participants

Reaction Steps

The 2-bromo-3-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (10.4 g, 27.7 mmol, prepared using A from Preparation #4 with ethynyltrimethylsilane, Q, A with 2-amino-3,5-dibromo-6-methylpyrazine [WO2008/083070, Example 29, Part B] and B) in DMF (125 mL) was treated with KOH (1.87 g, 33.3 mmol) at rt. The mixture was stirred for about 10 min and iodine (7.74 g, 30.5 mmol) was added over about 15 min in two equal portions. The mixture was stirred for about 45 min then NaH (60 wt % in mineral oil, 1.33 g, 33.3 mmol) was added in portions over about 5 min. The mixture was stirred for about 10 min then SEMCl (5.17 mL, 29.1 mmol) was added. The mixture was stirred for about 30 min then the solvents were removed under reduced pressure. The material was partitioned between EtOAc (200 mL) and water (200 mL) containing AcOH (3.18 mL, 55.5 mmol). The layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organics were washed with water (2×100 mL) then brine (100 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was dissolved purified with an 80 g silica gel column and eluted with 9:1 Heptane/EtOAc to give 2-bromo-7-iodo-3-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (12.7 g, 73%): LC/MS (Table 2, Method g) Rt=1.91 min; MS m/z 630 (M+H)+.

Provenance & Evidence