Syntheses Of Fomepizole And Axitinib

Acute alcohol intoxication shows serious inhibition on the cerebral cortex and subcortical central nervous system, lead to respiration, circulation failure, and even death. Therefore, it is important to take effective means of emergency treatment. The main purpose is to study and optimize the synthetic route of an alcohol dehydrogenase inhibitor-4-methyl pyrazole, which is suitable for industrial production.Fomepizole, was approved for the treatment of real or suspected ethylene glycol(antifreeze) and methanol poisoning in the US in 1997 and 2000. In addition, 4-methyl pyrazole can also be used for alcoholism by combing with ADH.Fomepizole was produced by mixing hydrate and methacrolein together. The add to the mixture of 70% H2SO4 and KI in 160 ?. When adding is completed, heat to remove water. The yield is about 80%.During this process,starting materials were added by constant pressure funnel, instead of syringe. Operation was more convenient, and the process showed higher yield with lower cost. Applying this process conditions, phosphates and nitrates were odorless, stable, uneasy absorption of moisture, and high safety index, which can be used as a therapy drug, taken before drinking.Axitinib(Inlyta), was developed by Pfizer, as an oral multi-targeted tyrosine kinase inhibitor. It was approved for the treatment of metastatic renal cell carcinoma in 2012 by United States FDA. The synthetic route chooses 2-Methyl-5-nitro-phenylamine as starting material, after two-step diazotization forms 6-iodo-indazole; Then the coupling reaction between 6-iodoindazole and 2-mercapto-N-methylbenzamide is carried out in the presence of a catalyst, a base and a suitable solvent. Finally, the target molecule will be obtained by coupling the indazole with activated substituent X with 2-vinylpyridine.Using these three starting materials, the process to synethses axitinib is easy to carried out.