4-Fluoroaniline → 1,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)amino]-3-pyridinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

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Reaction Conditions

Reaction Steps

BINAP (0.041 g, 0.0654 mmol), cesium carbonate (0.213 g, 0.654 mmol) and palladium acetate (0.009 g, 0.0436 mmol) were combined in dioxane (1 mL) and sonicated for 1 h under an argon atmosphere. To the red mixture was added 4-fluoroaniline (0.053 g, 0.479 mmol) and 1,1-dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D54) (0.2 g, 0.436 mmol). The mixture was stirred at 60° C. for 1 h, the solvent was removed under vacuum and the residues partitioned between EtOAc and water. The EtOAc layer was dried and concentrated. The crude product was purified by chromatography. Elution with a 0-70% EtOAc/petroleum ether gradient yielded the title compound as a pale yellow oil (0.110 g). δH (CDCl3, 400 MHz) 8.10 (1H, m), 7.40 (1H, dd), 7.25 (3H, m), 7.02 (4H, m), 6.92 (1H, s), 6.43 (1H, d), 4.18 (1H, br.s), 3.80 (1H, d), 3.48 (3H, s), 3.48 (1H, d), 3.36 (1H, d), 3.10 (1H, td), 2.70 (1H, d), 2.52 (1H, d), 2.10 (1H, m), 1.98 (1H, m), 1.85 (1H, br.s), 1.45 (9H, s), 1.20 (3H, d). MS (ES): MH+ 534.3.

Provenance & Evidence