Cesium carbonate → (S)-tert-butyl (1-((9-(4-fluorophenyl)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

(S)-tert-Butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (150 mg, 0.297 mmol) (prepared as described in Example 3, Part A) 4-fluorophenylboronic acid (49.9 mg, 0.357 mmol), Cs2CO3 (291 mg, 0.892 mmol) and PdCl2(dppf)-CH2Cl2 adduct (12.14 mg, 0.015 mmol) in 1,4-dioxane (8 mL) and water (0.4 mL) was degassed with nitrogen gas for 5 min then heated at 80° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was taken up in dichloromethane (10 mL) and water (8 mL). The organic layer was separated, dried with sodium sulfate, filtered and concentrated under reduced pressure to afford (S)-tert-butyl (1-((9-(4-fluorophenyl)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.13 g, 0.09 mmol, 31% yield) as a brown gum. The material was carried forward without further purification. LC/MS, (ESI) m/z 520.4 [(M+H)+, calcd for C30H35FN3O4 520.25]; LC/MS retention time (method D): tR=1.08 min.

Provenance & Evidence