反応 #657318

反応方程式

2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

N-(4-bromopyridin-2-yl)propanamide

Na2CO3

→

N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide

収率 23.5%

溶媒

1,4-dioxane

反応条件

後処理

1. 1
   その他The reaction mixture is flushed for 5 mins with argon
2. 2
   その他sealed
3. 3
   温度After cooling
4. 4
   workup.ADDITIONthe reaction mixture is diluted with EtOAc
5. 5
   洗浄washed with water
6. 6
   乾燥The combined organic phase are dried over Na2SO4
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

実験手順

150 mg of 2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (0.419 mmol, 1.1 eq.) and 87 mg of N-(4-bromopyridin-2-yl)propanamide (0.381 mmol, 1 eq.) are dissolved in 1.5 ml of 1,4-dioxane. To this solution are added 22 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.03 mmol, 0.08 eq) and a aqueous solution of Na2CO3 (5 eq, 0.952 ml). The reaction mixture is flushed for 5 mins with argon and then sealed. Next the mixture is heated for 15 mins at 120° C. in the microwave (CEM Explorer). After cooling, the reaction mixture is diluted with EtOAc and washed with water. The combined organic phase are dried over Na2SO4 and concentrated in vacuo. The crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 34 mg (21%) of N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide are obtained.

出典