Water → HCID 66749936, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 1-(2-bromo-5-pyridin-4-yl-3-thienyl)-6-chloro-3,4-dihydroisoquinoline-2(1H)-carboxylate (72.0 mg, 0.142 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxabolone)-pyrrazole (27.6 mg, 0.142 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (11.7 mg, 0.0142 mmol) and sodium carbonate (29 mg, 0.27 mmol) in 1,2-dimethoxyethane (3.0 mL, 29 mmol) and water (1.0 mL, 56 mmol) was heated at 95° C. for 4.5 h. A LCMS showed the desired product together with unreacted starting material. Additional [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (11.7 mg, 0.0142 mmol) 3-(4,4,5,5-Tetramethyl-1,3,2-dioxabolone)-pyrrazole (56 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol), sodium carbonate (100 mg, 0.9 mmol) and 1,2-dimethoxyethane (3.0 mL, 29 mmol) were added. The mixture was heated at 100° C. for another 4 h. The mixture was dry-loaded onto silica gel and purified by chromatography to afford tert-butyl 6-chloro-1-[2-(1H-pyrazol-5-yl)-5-pyridin-4-yl-3-thienyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate (41 mg, 58%). LCMS AA ES+ 493.2, 495.1.

Provenance & Evidence