Sodium hydride → HCID 89815042, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of sodium hydride 60% (0.330 g, 13.75 mmol) in 8 mL DMF was cooled to 0° C. and was treated with 4-methyl-1H-imidazole (0.676 g, 8.23 mmol). After stirring for 40 minutes, 1-bromo-2-fluoro-4-(trifluoromethyl)benzene (1.180 ml, 8.23 mmol) was added, and the reaction mixture was heated to 120° C. for 90 minutes. At this point Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.291 g, 0.412 mmol), isoquinolin-5-ylboronic acid (1.424 g, 8.23 mmol), potassium phosphate (6.99 g, 32.9 mmol), 16 mL dioxane and 12 mL water were added, and the reaction mixture was heated to 120° C. overnight. The reaction mixture was poured into saturated NaHCO3 solution and was extracted with DCM. The organics were concentrated then purified by reverse phase column chromatography [RediSep Gold C18 150 g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding 5-(2-(4-methyl-1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)isoquinoline (1.435 g, 4.06 mmol) as an about 4:1 mixture of isomers.

Provenance & Evidence