Cesium carbonate → HCID 68660645, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-(4-fluorophenyl)-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (1.13 g, 3.08 mmol), and tert-butyl 6-chloropyridazin-3-yl(methyl)carbamate (751 mg, 3.08 mmol) in DMF (15 mL) and water (3 mL) was added cesium carbonate (4.01 g, 12.3 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg, 0.06 mmol). The reaction flask was evacuated and back filled with nitrogen. After heating the reaction mixture at 85° C. for 4 hours, it was cooled to ambient temperature then partitioned between ethyl acetate (300 mL) and water (150 mL). The organic layer was washed with water and brine then dried over sodium sulfate. Concentration in vacuo gave the crude material which was purified by flash column chromatography to give tert-butyl 6-(4-(4-fluorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridazin-3-yl(methyl)carbamate (1.24 g, 90%) as an orange/brown foam: 1H NMR (CDCl3, 500 MHz) δ 8.12 (d, J=9.5 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 7.75-7.70 (m, 2H), 7.19 (dd, J=8.8 Hz, 5.0 Hz, 2H), 7.01-6.97 (m, 3H), 4.30 ((brs, 1H), 3.82 (d, J=14.5 Hz, 1H), 3.71 (d, J=14.5 Hz, 1H), 3.61 (s, 3H), 3.08-3.05 (m, 1H), 2.59 (dd, J=11.5 Hz, 8.0 Hz, 1H), 2.46 (s, 3H), 1.56 (s, 9H); ESI MS m/z 449 [M+H]+.

Provenance & Evidence