Development of a Scalable and High-yield Process for the Synthesis of Decitabine

Introduction: This research article focuses on the development of an alternate convergent approach for the synthesis of decitabine to increase productivity, such as superior yields, improved reaction conditions, and mild reagents that facilitate the creation of the target compound. The targeted compound decitabine is a chemotherapeutic drug used as medication for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and there were very few reports of its synthesis. Methods: Decitabine (4) was synthesized by reacting deoxyribose (1) and N-(trimethylsilyl)-4- (trimethylsilyloxy)-1, 3, 5-triazin-2-amine (2) under tin tetrachloride in dichloro methane. Results: The methodology was used to synthesize and improve the quality of the Decitabine drug substance by removing the formed impurities such as mono and ditoluoyl derivatives. Discussion: This synthesis and purification approach produces highly pure decitabine in good yields and allows the techniques to be scaled up with optimization. Conclusion: Our team produced the decitabine with a 95% purity and 65% yield; by treating it with dry methanol, we were able to increase the purity to >99%.