Improved Synthesis Process of Pivotal Intermediate of SKI2496 in Kilogram Scale
- Author:
Zhi-Xin DING
1
Author Information
- Publication Type:Journal Article
- Keywords: Drug synthesis; GnRH antagonists; Uracil
- From: Chinese Pharmaceutical Journal 2018;53(20):1718-1721
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To establish a preparation process of pivotal intermediate of SKI2496, which is low-cost, environmental-friendly and suitable for industrialization as well. METHODS: 1-(2-Fluoro-6-(trifloromethyl)benzyl)urea(2) was synthesized from 2-fluoro-6-(trifluoromethyl)benzylamine(1) with urea,followed by aminolysis with t-butyl acetoacetate and cyclization to give 1--6-methylpyrimidine-2,4(1H,3H)-dione(4).Finally,the title product was obtained via bromation and condensation reaction with piperazine. RESULTS: The synthetic process included four steps with an overall yield of 44.6%(based on compound 1) and its structure was confirmed by 1H-NMR and MS. CONCLUSION: The process is easy to operate, safe and suitable for industrial production.
