3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline → (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine

Participants

Reaction Conditions

Reaction Steps

(R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (400 mg, 1.45 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (265 mg, 1.31 mmol), Cesium carbonate (709 mg, 2.18 mmol), Palladium(II) acetate (32.6 mg, 0.15 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (168 mg, 0.29 mmol) were added to a microwave vial then dioxane (18 mL) was added. The reaction mixture was flushed with argon and then heated at 140°C for 60 min in a MW. The reaction mixture was filtered through celite and concentrated. The crude product was purified by silica flash chromatography using a gradient of methanol (0 to 5%) in dichloromethane. Not pure enough. The product was purified further with preparative chromatography. The productcontainíng product was collected and the methanol was evaporated off. The wather phase was extracted three times with dichloromethane, dried (Na2SO4) and concentrated giving (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine (195 mg, 30.4 %) as a dry film.

Provenance & Evidence