Cesium carbonate → 7-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,5-dichloro-N-methylpyrimidin-4-amine (1 mmol), 7-amino-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (222 mg, 0.94 mmol), cesium carbonate (0.65 g, 2 mmol), XantPhos (17 mg, 0.03 mmol) and Pd2(dba)3 (5 mg, 0.02 mmol) in dioxane (3 mL) was sonnicated in an ultrasonic bath for 1 min. The mixture was then degassed under a stream of nitrogen for 5 min. The tube was sealed and the reaction was heated at 100° C. for 18 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL). The organic layer was washed with water and the combined aqueous extracts were further washed with ethyl acetate. The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) gave 7-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (30 mg, 15%). LCMS (10 cm_ESCI_Formic_MeCN): [MH+]=378 at 2.77 min. 1H NMR δ (ppm)(400 MHz, d6-DMSO): 8.05 (1H, s), 7.98 (1H, s), 7.54 (1H, s), 7.28 (1H, d, J=5.2), 6.85 (1H, s), 3.93 (3H, s), 3.66 (3H, s), 2.91 (3H, d, J=4.6), 1.41 (6H, s).

Provenance & Evidence