反应详情

温度

80 °C

A mixture of (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (17) (Scheme 9; 0.138 g, 0.314 mmol), (S)-tert-butyl 2-(5-(4-iodophenyl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate 8 (0.141 g, 0.321 mmol), NaHCO3 (0.110 g, 1.31 mmol) and Pd(PPh3)4 (0.024 g, 0.0208 mmol) in a mixture of DME (3 mL) and H2O (1 mL) was heated at 80° C. under Ar for 12 hours. The cooled mixture was diluted with ethyl acetate/H2O, the layers separated and the aqueous phase was re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine) and dried (Na2SO4) and filtered and the solvent was removed in vacuo. The resulting residue was purified by flash chromatography (hexane:ethyl acetate, 2:1 and then ethyl acetate:methanol, 9:1) to give (S)-tert-butyl 2-(5-(4′-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate (19) (0.084 g, 43%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.01, 12.69, 12.20, 11.91, 11.85 (s, 1H), 7.63-7.85 (m, 8H), 7.50-7.56 (m, 1H), 6.52 (s, 1H), 4.75-4.94 (m, 2H), 3.42-3.58 (m, 2H), 3.30-3.39 (m, 2H, partially obscured by H2O signal), 2.10-2.28 (m, 2H), 1.81-2.01 (m, 6H), 1.40 (s, 7H), 1.20-1.23 (m, 6H), 1.13-1.15 (m, 5H). LCMS: Anal. Calcd. for C36H44N6O4: 624. found: 625 (M+H)+.

1. customthe layers separated
2. extractionthe aqueous phase was re-extracted with ethyl acetate (2×)
3. washThe combined organic layers were washed (H2O, brine)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. customthe solvent was removed in vacuo
7. customThe resulting residue was purified by flash chromatography (hexane