Sodium Bicarbonate → HCID 178425145, compound

Participants

Reaction Conditions

Reaction Steps

6-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one (200 mg, 0.881 mmol) (J. Med. Chem. 2003; 46; 9; 1627-1635), bis(pinacolato)diboron (268 mg, 1.057 mmol), Pd(dppf) (35.7 mg, 0.044 mmol) and potassium acetate (259 mg, 2.64 mmol) were suspended in 1,4-Dioxane (8 mL), and stirred with heating at 100° C. for 1 h. After cooling to room temperature, 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 (329 mg, 0.881 mmol), bis(triphenylphosphine)palladium(II) chloride (71.9 mg, 0.088 mmol) and sodium bicarbonate (222 mg, 2.64 mmol) were added, followed by DME (5 mL) and water (3 mL). The reaction mixture was irradiated (microwave) at 120° C. for 2 h. The reaction mixture was cooled to room temperature and filtered through Na2SO4. The contents were purified directly by silica gel chromatography (eluent: 5% MeOH/CH2Cl2) to furnish the desired product as a grey solid after evaporation and preciptation from warm EtOAc/MeOH (1:9). The product was collected as 55 mg (13%). LCMS E-S (M+H)=486.3 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (br. s., 1 H), 10.74 (s, 1 H), 8.99 (d, J=2.27 Hz, 1 H), 8.93 (t, J=4.93 Hz, 1 H), 8.44 (d, J=1.77 Hz, 1 H), 8.37 (s, 1 H), 8.16 (s, 1 H), 5.91 (s, 1 H), 5.29-5.40 (m, 1 H), 4.42 (d, J=5.05 Hz, 2 H), 3.04 (t, J=7.58 Hz, 2 H), 2.53-2.62 (m, 2 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 1.54 (d, 6 H).

Provenance & Evidence