Dichloromethane → (S)-1-cyclopropyl-3-(3-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-(2-chloro-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 12) (150 mg, 0.55 mmol) and 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (212 mg, 0.69 mmol) in DME/EtOH/H2O (7/3/2) (2 mL) was added [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (22 mg, 0.027 mmol) and Cs2CO3 (538 mg, 1.65 mmol). The reaction mixture was then heated by microwave at 115° C. for 45 min. The crude reaction mixture was partitioned between EtOAc (25 ml) and water (25 ml). The organic layer was recovered, passed through a hydrophobic frit and the solvent removed in vacuo. Residue was then purified by preparative HPLC at low pH to afford a yellow solid (25 mg, 0.06 mmol, 11%).

Provenance & Evidence