Cesium carbonate → Methyl 4-(3-amino-6-cyclopropylpyrazin-2-yl)-2-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (for synthesis see Example 34, Step 2) (300 mg, 0.920 mmol) in toluene (10 mL) and water (1 mL) was added potassium cyclopropyl trifluoroborate (408 mg, 2.76 mmol), di(1-adamantyl)-n-butylphosphine (66.0 mg, 0.184 mmol), cesium carbonate (1499 mg, 4.60 mmol), and palladium(II) acetate (20.65 mg, 0.092 mmol). The reaction mixture was heated in heating block at 100° C. overnight. The reaction mixture was quenched with sat. NH4Cl and extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude was purified by flash chromatography (0 to 80% EtOAc in heptane) yielding methyl 4-(3-amino-6-cyclopropylpyrazin-2-yl)-2-fluorobenzoate (250 mg, 90%). LCMS (m/z): 288.2 (MH+), 0.756 min.

Provenance & Evidence