In this paper,the synthesis method of Dinaciclib,a small molecule inhibitor of cyclin kinase(CDKs),was improved.An important intermediate 5,7-dichloro-3-ethylpyrazolo[1,5-a]pyrimidine(4)was synthesized from 3-amino-4-bromopyrazole(1)and 3-aminomethylpyridine(5)by coupling,cyclization and chlorination.An other important intermediate 4-aminomethylpyridine-N-oxide dihydrochloride(8)was obtained by substitution and oxidation of 3-aminomethylpyridine(5).(5-Chloro-3-ethyl-pyrazolo[1,5-a]pyrimidin-7-yl)-(1-oxo-pyridine-3-methylene)-amine(9)was obtained by substitution reaction of compound 4 with compound 8.The target product Dinaciclib,was obtained by substitution reaction of compound 9 with(S)-(-)-2-piperidineethanol.The target product was detected by HPLC,and the purity was 98％.The total yield was 75％based on 4.Compared to the original research route,the improved process route reduced costs,increased yields,and shortened route time,making it suitable for large-scale industrial production.
维普
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