Cesium carbonate → HCID 57636053, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-ylmethyl)-amine (200 mg, 0.62 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl-boronic acid (190 mg, 0.94 mmol), and Cs2CO3 (0.51 g, 1.6 mmol) in ethylene glycol dimethyl ether (10 mL) and water (2 mL) is degassed by bubbling with Ar gas for 5 minutes, and treated with tetrakis(triphenylphosphine)palladium (0) (36 mg, 0.03 mmol) at room temperature. The mixture is heated at 85° C. for 6 h. The mixture is diluted with H2O (20 mL), and extracted with EtOAc (20 mL). The aqueous layer is separated, acidified to pH 3 with 1M HCl solution, and extracted with EtOAc (2×30 mL). The extracts are dried (MgSO4), filtered, and concentrated. The residue is chromatographed on SiO2 (70% EtOAc in heptane) to afford 2-(3-{2-methoxy-6-[(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (190 mg, Example 92). LCMS: RT=2.59 minutes; MS: 449 (M+H). IC50=278 nM

Provenance & Evidence