反応 #42068

反応方程式

2-chloro-1-methylpyridinium iodide

4-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethylbenzoic acid

4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]aniline

N,N-diisopropyl-N-ethylamine

→

objective compound

収率 55.2%

4-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethyl-N-{4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]phenyl}benzamide

収率 55.2%

溶媒

water

N,N-dimethylformamide

反応条件

後処理

1. 1
   workup.STIRRINGby stirring at room temperature for 1 hour
2. 2
   抽出followed by extraction with ethyl acetate
3. 3
   workup.ADDITIONTwo hundred ml of saturated sodium hydrogen carbonate was added to the aqueous layer
4. 4
   抽出the mixture was further extracted with ethyl acetate
5. 5
   乾燥dried over anhydrous magnesium sulfate
6. 6
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
7. 7
   その他The residue was purified by column chromatography
8. 8
   洗浄the crude crystals were washed with diethyl ether-ethyl acetate

実験手順

Under an argon atmosphere, 1.71 g of 4-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethylbenzoic acid (Reference Example 14) was dissolved in 14 ml of anhydrous N,N-dimethylformamide and 1.56 g of 2-chloro-1-methylpyridinium iodide was added, followed by stirring at room temperature for 10 minutes. 1.50 g of 4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]aniline (Reference Example 18) and 1.13 ml of N,N-diisopropyl-N-ethylamine were added in turn, followed by stirring at room temperature for 1 hour. 300 ml of water was added to the reaction solution, followed by extraction with ethyl acetate. Two hundred ml of saturated sodium hydrogen carbonate was added to the aqueous layer and the mixture was further extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography and the crude crystals were washed with diethyl ether-ethyl acetate to obtain 1.68 g of the objective compound as pale yellow crystals.

出典