Water → HCID 56598142, compound

Participants

Reaction Conditions

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 [4-(acetylamino)phenyl]boronic acid (57.5 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.7 mg, 0.010 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 light brown mixture was heated at 110° C. for 2.5 h. After cooling, 2 mL of water was added to the dark grey mixture and solids that precipitated were filtered. EtOAc was added, the mixture was heated and some hexanes were added. The solids were filtered, dissolved in DCM/MeOH (1:1) and 1 mL of DMF. The contents were pre-absorbed onto silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with MeOH, and the solids that precipitated were filtered, washed with hexanes and dried to afford the title compound (55 mg, 52%) as a white solid. LCMS E-S (M+H)=473.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (s, 1 H), 10.18 (s, 1 H), 8.93 (t, J=4.93 Hz, 1 H), 8.35 (s, 1 H), 8.22 (m, J=8.84 Hz, 2 H), 8.13 (s, 1 H), 7.76 (m, J=8.84 Hz, 2 H), 5.91 (s, 1 H), 5.28-5.37 (m, 1 H), 4.41 (d, J=4.80 Hz, 2 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 2.09 (s, 3 H), 1.54 (d, J=6.82 Hz, 6 H).

Provenance & Evidence