Ethyl Acetate → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (4'-amino-3-cyclohex-1-enyl-biphenyl-4-yl)-amide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (as prepared in the Example 11, step (f), 30 mg, 0.060 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (14.4 mg, 0.066 mmol) and Pd(PPh3)4 (7 mg, 0.006 mmol) in 1 mL of 1,4-dioxane was added 2.0 M aq Na2CO3 solution (0.24 mL, 0.48 mmol). The resulting mixture was stirred at 80° C. for 3 h under Ar, and then cooled to RT. Treated with 50 μL of EtOAc, the mixture was washed with H2O (2×20 mL), brine (10 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (20% EtOAc/hexane) gave 16 mg (85%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 9.76 (s, 1H), 8.37 (d, 1H, J=8.6 Hz), 7.78 (s, 1H), 7.43-7.47 (m, 3H), 7.35 (d, 1H, J=2.1 Hz), 6.84 (d, 2H, J=8.5 Hz), 5.97 (s, 2H), 5.89 (m, 1H), 3.67 (t, 2H, J=8.2 Hz), 2.25-2.34 (m, 4H), 1.77-1.90 (m, 4H), 0.98 (t, 2H, J=8.2 Hz), 0.01 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C29H35N5O2Si, 514.3 (M+H), found 514.1.

Provenance & Evidence