1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Participants

Reaction Steps

Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I7) (0.195 g, 0.333 mmol) was dissolved in dry THF (10 mL) and dry DMF (2 mL) under an atmosphere of nitrogen. To the solution were added 1-hydroxybenzotriazole (0.049 g, 0.37 mmol) and EDCI (0.070 g, 0.37 mmol) and N,N-diisopropylethylamine (0.232 mL, 1.33 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. Ammonium carbonate (0.128 g, 1.332 mmol) was added in one portion, and the reaction was stirred room temperature for 20 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (70 mL) and sat. aq. NaHCO3 (70 mL). The layers were separated and the organic layer was washed with water (70 mL), brine (70 mL), dried (MgSO4), filtered and concentrated in vacuo to give the crude product which was purified by silica gel chromatography (Biotage Isolera, 12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-10% methanol in EtOAc) to give the title compound (I8) (0.133 g, 68% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.01 (s, 1H), 8.61 (s, 1H), 7.65-7.56 (m, 2H), 7.44 (s, 1H), 7.26-7.13 (m, 4H), 6.98-6.89 (m, 3H), 3.52-3.41 (m, 6H), 3.13-2.95 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.18 min; m/z 585.3 [M+H]+.

Provenance & Evidence