반응 #42068

반응 방정식

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

수율 55.2%

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

수율 55.2%

용매

water

N,N-dimethylformamide

반응 조건

후처리

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

실험 절차

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.

출처