1. Field of the Invention
The invention relates to the synthetic methods and manufacture procedures for (methyl-d3)amine and salts thereof.
2. Description of Related Art
(Methyl-d3)amine and the hydrochloride thereof, the important intermediates for chemical synthesis, can be used to make medicinal compounds.
For example, the ω-diphenylurea derivatives are known as the compounds with c-RAF kinase inhibition activity. Initially, ω-diphenylurea compounds, such as Sorafenib, were firstly found as the inhibitors of c-RAF kinase. The other studies had shown that they could also inhibit the MEK and ERK signal transduction pathways and activities of tyrosine kinases including vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor receptor-3 (VEGFR-3), and platelet-derived growth factor receptor-β (PDGFR-β) (Curr Pharm Des 2002, 8, 2255-2257). Therefore, it is called multi-kinase inhibitor which possesses dual anti-tumor effects.
Sorafenib (trade name Nexavar), a novel oral multi-kinase inhibitor, was developed by Bayer and Onyx. In December 2005, based on its outstanding performance in phase III clinical trials for treating advanced renal cell carcinoma, Sorafenib was approved by FDA for treating advanced renal cell carcinoma. It was marketed in China in November 2006. However, Sorafenib has various side-effects, such as hypertension, weight loss, rash and so on.
(Methyl-d3)amine is used during the preparation of sorafenib derivatives. However, the synthetic steps or the current preparation processes are relatively complex, or the cost is high. Therefore, development of some simple, highly efficient, and/or low cost methods for preparing (methyl-d3)amine and salts thereof is needed.