Sodium t-butoxide → Tert-butyl 4-(4-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)amino)-3-nitrophenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

1-(6-chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea (175 g, 0.34 mmol), tert-butyl 4-(4-amino-3-nitrophenyl)piperazine-1-carboxylate (90 g, 0.28 mmol), Pd2(dba)3 (13 g, 0.014 mmol), Brettphos (13 g, 0.028 mmol) and sodium tert-butoxide (54 g, 0.56 mmol) were placed in a reaction vial (2 to 5 ml) and purged with nitrogen. Toluene (1.0 ml) was added and nitrogen was bubbled for 5 min then the reaction mixture was heated at 100° C. overnight. Heating was stopped and cooled to room temperature. The reaction mixture was filtered through pad of Celite®. The filtrate was evaporated and resulting material was purified by flash chromatography on silica eluting with 20% to 70% EtOAc/Hexane to afford the title compound (102.4 mg, yield: 45%). 1H-NMR (400 MHz, CDCl3) δ 0.01 (s, 9H) 0.85-0.98 (m, 2H) 1.50 (s, 9H) 3.03 (s, 3H) 3.17 (br. s., 4H) 3.56-3.66 (m, 4H) 3.75-3.97 (m, 8H) 5.22 (s, 2H) 6.50 (s, 1H) 6.95 (s, 1H) 7.65 (s, 1H) 8.46 (s, 1H)

Provenance & Evidence