Diisopropylethylamine → 2-[(1R)-2-amino-1-phenylethyl]-5-(4-chloro-1-methyl-1H-pyrazol-5-yl)isoindolin-1-one

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Reaction Steps

A mixture of 1-methyl-4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (69.5 mg, 0.334 mmol), bis(tri-t-butylphosphine)palladium (14 mg, 0.028 mmol), tert-butyl [(2S)-2-(5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2-phenylethyl]carbamate (120.0 mg, 0.2782 mmol) and N,N-diisopropylethylamine (145 μL, 0.835 mmol) in 1,4-dioxane (1000 μL) and water (50 μL) was microwaved at 110° C. for 15 minutes. After filtering and concentration, the residue was purified by prep.—HPLC (pH=10). To the purified intermediate was added methylene chloride (0.5 mL) and trifluoroacetic acid (0.5 mL). The solution was stirred at room temperature for 1 h. After concentration, the residue was neutralized with TEA (0.5 mL) then concentrated. Purification by prep.—HPLC (pH=10) afforded 25.6 mg (25% yield) of the desired product as white solid. LC-MS found: 367.1 (M+H)+.

Provenance & Evidence