تفاعل #42068

معادلة التفاعل

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

المردود 55.2%

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

المردود 55.2%

المذيبات

water

N,N-dimethylformamide

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر