反応 #1017543

反応方程式

(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine)

N-((4R,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide

5-chloropicolinamide

cesium carbonate

→

N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

収率 71.4%

反応条件

後処理

1. 1
   その他The flask was evacuated under vacuum
2. 2
   その他flushed with nitrogen
3. 3
   workup.ADDITIONDioxane (0.5 mL) was then added
4. 4
   温度The reaction mixture was cooled to RT
5. 5
   ろ過filtered through celite
6. 6
   洗浄washed with EtOAc
7. 7
   濃縮The filtrate was concentrated
8. 8
   その他the residue was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
9. 9
   洗浄eluting with a gradient of 0% to 30% EtOAc in hexane

実験手順

A round-bottomed flask was charged with Pd2(dba)3 (2.91 mg, 3.17 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.35 mg, 0.013 mmol), N-((4R,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (21 mg, 0.042 mmol), 5-chloropicolinamide (9.61 mg, 0.061 mmol), and cesium carbonate (34.5 mg, 0.106 mmol). The flask was evacuated under vacuum and then flushed with nitrogen. Dioxane (0.5 mL) was then added and the reaction was stirred in a 90° C. oil bath for 10 h. The reaction mixture was cooled to RT, filtered through celite and washed with EtOAc. The filtrate was concentrated and the residue was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide (17 mg, 0.030 mmol, 70.2% yield) as white solid. MS m/z=572, 574 M+, Calculated for C24H16ClF6N5O3: 571.86.

出典