In order to effectively control the quality of Saxagliptin and establish its quality standards,(S)-2-(adamantan-1-yl)-2-((R)-2-hydroxy-1-phenylethyl)aminoacetic acid hydrochloride was used as the starting material.After Pd/C catalyzed hydrogenation,condensation with di-tert-butyl dicarbonate,oxidization by potassium permanganate,Saxagliptin impurity tert-butyl(S)-2-[1-(3-dimethylaminopropyl)-3-ethylureido]-1-[(1R,3R,5R,7S)-3-hydroxyadamantan-1-yl]-2-oxoethyl)carbamate(5)was synthesized from rearrangement reaction with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride,and purification with an overall yield of about 37.8% and a purity of 98.9% .Their structures were confirmed by 1H NMR,13C NMR and HRMS.The conditions for synthetic process were optimized.This synthesis process is reasonable and feasible,the reaction conditions are mild,and the purity is high.It can be used as the impurity reference substance for the quality control of Saxagliptin.
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