Study On The Synthesis Of D Series Compounds For Small Molecule Inhibitors Targeting ALK

Lung cancer is the highest morbidity and mortality cancer in the world,which is a serious threat to human health.Currently targeted therapy as the most effective treatment,can kill tumor cells specifically and not affect the surrounding tissue cells.In recent years,the development of non-small cell lung cancer drug has made some progress.The design and development of anaplastic lymphoma kinase targeting drug in the treatment of non-small cell lung cancer has made important significance.But some resistance have taken after patients taking some drugs,therefore designing and developing new and effective drugs is very necessary.In view of the fact that anaplastic lymphoma kinase plays an important role in the development and progression of various tumors,this paper designed three specific anaplastic lymphoma kinase small molecule inhibitors[5-chloro-N₄-?2-?isopropyl sulfonyl?phenyl?-N2-?2-phenylimidazo[1,2-c]pyrimidin-7-yl?pyrimidine-2,4-diamine?compoundD1?,5-chloro-N4-?2-?isopropylsulfonyl?phenyl?-N2-?6-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl?pyrimidine-2,4-diamine?compoundD2?,8-?4-?4-?5-chloro-4-??2-?isopropylsulfonyl?phenyl?amino?pyrimidin-2-yl?piperazin-1-yl?piperidin-1-yl?quinazolin-4?3H?-one.?compound D3?.].It is aiming to use anaplastic lymphoma kinase as the target for the treatment of.non-small cell lung cancers.ThesynthesisofD1,D2andtheintermediateCompound5-chloro-N-?2-?isopropylsulfonyl?phenyl?-2-?4-?piperidin-4-yl?piperazin-1-yl? pyrimidin-4-amine hydrochloride D3-I of D3 was also studied,and the structure was characterized by ¹H NMR,¹³C NMR,high resolution mass spectrometry and infrared spectroscopy.The compound D1 was synthesized from 2,4-diaminopyrimidine by ring-forming reaction and Buchwald-Hartwig coupling reaction,and the total yield was 38%.Compound D2 was obtained from 5-bromo-2-fluoropyridine by substituting,ringing,Suzuki coupling and Buchwald-Hartwig coupling to give the target product with a total yield of 23%.The intermediate Compound D3-I of D3 was synthesized from N-Boc-piperazine by Buchwald-Hartwig coupling,amino deprotection,reductive amination,salt formation reaction to give the target product with a total yield of 49%.