Water → HCID 56598004, compound

Participants

Reaction Steps

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (80 mg, 0.21 mmol) and [6-(dimethylamino)-3-pyridinyl]boronic acid (53.3 mg, 0.32 mmol) in DME/water (3 mL:1 mL). PdCl2 (dppf)-CH2Cl2 adduct (8.7 mg, 0.011 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (53.9 mg, 0.64 mmol) was added, the vessel was sealed, and the insoluble green mixture was irradiated (microwave) at 150° C. for 20 min. After cooling, 2 mL of water was added to the dark green mixture and solids that precipitated were filtered. EtOAc was added, the mixture was heated and some hexanes were added. Solids were filtered, dissolved in DCM/MeOH (1:1), and filtered through a pad of silica gel and the filtrate was evaporated. The residue was dissolved in DCM and purified by SiO2 chromatography (eluent: gradient of 0 to 90:10 DCM/MeOH) to afford a residual oil that was triturated with EtOH/EtOAc (1:1). The resultant solid was filtered and dried to afford the title compound (46 mg, 45%) as a yellow solid. LCMS E-S (M+H)=460.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (s, 1H), 9.02 (d, J=2.27 Hz, 1H), 8.87 (t, J=4.67 Hz, 1H), 8.36 (dd, J=8.84, 2.53 Hz, 1H), 8.31 (s, 1H), 8.08 (s, 1H), 6.79 (d, J=8.84 Hz, 1H), 5.91 (s, 1H), 5.25-5.34 (m, 1H), 4.40 (d, J=4.80 Hz, 2H), 3.12 (s, 6H), 2.23 (s, 3H), 2.13 (s, 3H), 1.53 (d, J=6.57 Hz, 6H).

Provenance & Evidence