Cesium carbonate → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

Participants

Reaction Conditions

Reaction Steps

Argon is bubbled through a mixture of (6-chloro-2-methoxymethyl-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine (200 mg, 0.58 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid [266 mg, 1.28 mmol, see Example 49(b) step 2], Cs2CO3 (1.56 g, 2.52 mmol), and tetrakis(triphenylphosphine)palladium (0) (69 mg, 0.06 mmol) in ethylene glycol dimethyl ether (4 mL) and water (1 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 16 hours the mixture is diluted with water (40 mL) and extracted twice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and evaporated. The residue is subjected to chromatography on silica gel eluting with 40% ethyl acetate:heptane to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [165 mg, 60%, Example 85] as a solid. LCMS RT=2.59 minutes, MS: 474 (M+H). IC50=2.7 nM

Provenance & Evidence