Reaktion #470
ord-62cd397fe6424e97abf226dd021d8df0
Reaktionsgleichung
Lösungsmittel
Reaktionsbedingungen
Vorschrift
A mixture of 5-(6-amino-2-methoxypyridin-3-yl)-1-methylpyridin-2(1H)-one (0.2 g, 0.86 mmol), 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.243 g, 0.86 mmol), Palladium(II) acetate (0.019 g, 0.09 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.050 g, 0.09 mmol) and Sodium tert-pentoxide (0.114 g, 1.04 mmol) in dioxane (1.5 mL) was heated by microwave irradiation to 120 °C for 30 min. The mixture was allowed to cool. DCM (5 mL) was added and the mixture was filtered through a short pad of Celite. The filtrate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-5% MeOH in DCM. The collected fractions were combined and the solvent was removed by rotary evaporation. The residue was submitted for separation by chiral SFC to yield 5-(2-methoxy-6-(4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-ylamino)pyridin-3-yl)-1-methylpyridin-2(1H)-one (0.055 g, 26.8 %) and 5-(2-methoxy-6-(4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-ylamino)pyridin-3-yl)-1-methylpyridin-2(1H)-one (0.051 g, 24.80 %). EN04155-91-001: 1H NMR in DMSO-d6 is consistent with desired product MS (m+1) = 476.1. HPLC Peak RT = 2.48 minutes is product. Purity = 97%. EN04155-91-002: 1H NMR in DMSO-d6 is consistent with desired product MS (m+1) = 476.1. HPLC Peak RT = 2.48 minutes is product. Purity = 98%.