Potassium Carbonate → Methyl 6-(2-((tert-butyldimethylsilyloxy)methyl)imidazo[1,2-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate

Participants

Reaction Conditions

Reaction Steps

6-bromo-2-((tert-butyldimethylsilyloxy)methyl)imidazo[1,2-a]pyridine (1.00 g, 2.93 mmol), bis(pinacolato) diborate (0.892 g, 3.51 mmol), Pd(dppf)Cl2 (86 mg, 0.12 mmol, 4 mol %), and KOAc (0.860 g, 8.76 mmol) were mixed together in a heat-gun dried flask. The flask was vacuumed and backfilled with argon before dioxane (9 mL) was added. Mixture was heated at 130° C. for ˜3 h until complete consumption of the starting bromide was observed. Reaction mixture was cooled to room temperature before H2O (0.90 mL), K2CO3 (1.20 g, 8.68 mmol), 6-chloro-5-ethyl-2-methoxynicotinate (0.673 g, 2.93 mmol) and fresh Pd(dppf)Cl2 (60 mg, 0.08 mmol, 3 mol %) were added. Reaction flask was resealed under argon and mixture was heated at 120° C. overnight and then cooled to room temperature. Water (10 mL) was added to the reaction mixture and product was extracted with DCM (3×20 mL). Combined organics were washed with NaCl (aqueous saturated, 20 mL) and dried over Na2SO4. Upon concentration of the solvent residue was purified by column chromatography (EtOAc/hexanes, 0-60% gradient). After concentration of the desired fractions, residue was treated with H2O (10-15 mL) and stirred vigorously for 30 min, solid was then filtered and washed with H2O. Upon drying methyl 6-(2-((tert-butyldimethylsilyloxy)methyl)imidazo[1,2-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate (1.00 g, 75%) was obtained as solid.

Provenance & Evidence