N-[5-Amino-2-(propan-2-yl)phenyl]acetamide → N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-propan-2-ylphenyl]acetamide

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In a 5 mL microwave reactor vial was charged with 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (0.070 g, 0.30 mmol), N-(5-amino-2-isopropylphenyl)acetamide (0.058 g, 0.30 mmol), Pd2(dba)3 (0.014 g, 0.01 mmol), Pd2(dba)3 (0.014 g, 0.01 mmol) and cesium carbonate (0.293 g, 0.90 mmol), the vessel was sealed with a microwave cap, and degassed and refilled with argon for 3 times. DMA (0.5 mL)was added via syringe. The resulting suspension heated at 140°C for 30mins in microwave. LCMS analysis showed product mass and byproduct. The reaction mixture was concentrated. 10% MeOH in DCM was added to the resulting residue to generate a brown suspension. This brown suspension was filtered to remove inorganic impurity. The filtrate was concentrated to give a brown crude product. This material was loaded on isco column (12g, DCM to 10% MeCNin DCM to 25% MeCN in DCM to 50%MeCN to 100% MeCM) and purified. Only 3mg of product was isolated. The ISCO column was saved. Some solid was presented on the top of the column. This solid was recovered, washed with water and dried under high vacuum at 60C to give N-(5-(3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-ylamino)-2-isopropylphenyl)acetamide (0.012 g, 10.29 %) as an offwhite solid.

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