1-Bromo-3-chloro-5-fluorobenzene → 8-(1-(3-chloro-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

온도

90 °C

To a mixture of 8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (350 mg, 1.01 mmol), cesium carbonate (1288 mg, 3.95 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (147 mg, 0.25 mmol) and 1-bromo-3-chloro-5-fluorobenzene (467 mg, 2.23 mmol) in degassed 1,4-dioxane (2ml), was added TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (69.6 mg, 0.08 mmol). The suspension was heated in a sealed container up to 95°C for 16hours. The reaction mixture was filtered through a short pad of dicalite, concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 0 to 8 % iPrOH in CH2Cl2. The solvent was evaporated to dryness to afford the 8-(1-(3-chloro-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (375 mg, 78 %). The product triturated with diethyl ether - CH2Cl2 (9-1) and the desired compound was filtered and dried to afford 320 mg of product P1 as a clear yellow solid. However the final sample product contain some diethyle ether which was removed under vacuum O/N before sample submission.

ORD 기록

ord-b3fb1d017e3744dea3ab3e0ecb0c58d8

출처 데이터셋

750 AstraZeneca ELN dataset

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