1,2-Dimethoxyethane → HCID 53316574, compound

Participants

Reaction Steps

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichlorophenyl)-ethyl]amine (0.24 g), 2-[4-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-methyl-propionic acid (0.4 g), Cs2CO3 (1.01 g) and tetrakis(triphenylphosphine)palladium (0) (100 mg) in water (20 mL)/DME (80 mL) is heated at 90° C. for 16 h. The solution is poured into water and extracted with EtOAc (2×200 mL). The organic layer is dried over sodium sulfate, filtered, evaporated in vacuo. The residue is chromatographed on silica gel eluting with EtOAc to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-4-fluoro-phenyl)-2-methyl-propionic acid (100 mg), which is dissolved in THF (4 mL) and treated with 4 N HCl in 1,4-dioxane (1 mL). The mixture is concentrated in vacuo and the residue is suspended in ether (25 mL). The solid is formed and filtered under nitrogen to afford 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-4-fluoro-phenyl)-2-methyl-propionic acid hydrochloride (67 mg, Example 99). MS: 478 (M+H); 1H NMR (300 MHz, NMR, CD3OD) □7.8, (d, 1H, J=0.3 Hz); 7.4 (m, 2H); 7.35 (s, 1H); 7-7.15 (m, 4H); 6.6 (s, 1H); 4.2 (s, 3H); 3.6 (m, 2H); 3.05 (t, 2H); 1.65 (s, 6H). IC50=0.5 nM

Provenance & Evidence