2-(Di-tert-butylphosphino)biphenyl → 2-[4-(4-Mesylpiperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Participants

Reaction Conditions

Reaction Steps

2-Amino-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Method 39 of WO 03/076436; 220 mg, 1 mmol), 1-bromo-4-(4-mesylpiperazinyl)benzene (WO 2001062742; 319 mg, 1 mmol), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 2 mol %), 2-(di-tert-butylphosphino)biphenyl (6 mg, 2 mol %) and sodium tert-butoxide (135 mg, 1.4 mmol) in anhydrous 1,4-dioxane (10 ml) was evacuated and refilled with nitrogen (3 times). The reaction was heated under nitrogen at 95° C. overnight before evaporating under reduced pressure. The residue was triturated with EtOAc (20 ml), filtered and re-evaporated to give a gum. Chromatography on silica gel with MeOH:DCM (2:98 to 5:95) gave the title compound as a yellow solid. (70 mg 15%). NMR: 1.39 (d, 6H), 2.47 (s, 3H), 2.92 (s, 3H), 3.17 (m, 4H), 3.26 (m, 4H), 5.70 (septuplet, 1H), 6.92 (d, 2H), 6.94 (d, 1H), 7.39 (s, 1H), 7.48 (d, 2H), 8.32 (d, 1H), 9.18 (s, 1H); m/z 456.

Provenance & Evidence