Hydrochloric Acid → HCID 58382225, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-bromo-7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (2.00 g, 3.86 mmol, Preparation #5) and PdCl2(PPh3)2 (0.406 g, 0.579 mmol) in DMF (25 mL) was degassed under reduced pressure and the solution was placed under an atmosphere of CO. MeOH (4.70 mL, 116 mmol) and TEA (2.15 mL, 15.4 mmol) were added and then the mixture was degassed under reduced pressure and the solution placed under an atmosphere of CO. The mixture was then heated to 95° C. under an atmosphere of CO maintained via a balloon for 6.5 h. The solvents were evaporated under reduced pressure then the material was dissolved in 1,4-dioxane (50 mL). Water (10 mL) and LiOH (0.65 g, 27 mmol) were added then the mixture was heated to 75° C. for 90 min. The mixture was cooled to rt and then most of the 1,4-dioxane was removed under reduced pressure. The mixture was treated with water (50 mL) and Et2O (50 mL). The layers were separated then the organic layer was extracted with water (4×50 mL). The combined aqueous extracts were acidified with aqueous HCl (5.0 N, 6.2 mL, 31 mmol) and then extracted with DCM (50 mL, 2×30 mL). The organics were combined and dried over anhydrous MgSO4 then filtered and concentrated under reduced pressure to give 7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-2-carboxylic acid (0.92 g, 49%): LC/MS (Table 2, Method a) Rt=2.63 min; MS m/z 484 (M+H)+.

Provenance & Evidence