Potassium Phosphate, Tribasic → 6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(5-isopropyl-1H-indazol-4-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine

Participants

Reaction Steps

Microwave was used to irradiated a solution of 2-chloro-6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine (30 mg, 0.099 mmol), crude 5-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (38.2 mg, 0.119 mmol), Pd(PPh3)4 (11.45 mg, 9.91 μmol) and K3PO4 (42.1 mg, 0.198 mmol) in 1,4-dioxane (0.5 mL) and H2O (0.05 mL) at 130° C. for 1 h under nitrogen. Additional Pd(PPh3)4 (22.90 mg, 0.020 mmol) was added to the mixture. Microwave was irradiated to the mixture at 130° C. for further 2 h under nitrogen. The mixture was diluted with brine and EtOAc. The organic layer was separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on 12 g of silica gel (eluent: DCM/MeOH=100:0 to 10:1) to give 6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(5-isopropyl-1H-indazol-4-yl)-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine: 1H NMR (400 MHz, CDCl3) δ ppm 9.98 (br s, 1 H), 7.76 (d, J=0.76 Hz, 1H), 7.45-7.51 (m, 2 H), 7.12 (s, 1 H), 5.65 (s, 1 H), 4.11 (s, 2 H), 3.75 (s, 3 H), 3.30-3.33 (app t, 2 H), 3.15-3.24 (m, 3 H), 2.30 (s, 3 H), 1.87-1.94 (m, 1 H), 1.25 (d, J=7.07 Hz, 6 H), 0.89-0.94 (m, 2 H), 0.72-0.76 (m, 2 H); MS (ESI+) m/z 427.33 (M+H)+.

Provenance & Evidence