Synthesis And Study On Amide Activator TBCC/TBCB And Imatinib

This paper consists of two parts:the first part is the synthesis and studying on TBCC/TBCB. The second part is the study on the technology of Imatinib. PartⅠ:In this part, New approaches have been developed here:4-methyl-benzoic acid first reacted with thionyl chloride, then with caprolactam, and last with N-bromosuccinimide to produce the 4-bromomethyl benzoyl caprolactam. Further, N, N, N-triethyl-4-[(hexahydro-2-oxo-1H-azepin-1-yl) carbonyl]-, Bromine (TBCB) was prepared through the reaction with triethylamine and 4-bromomethyl benzoyl caprolactam. The total yield was 60.6%.4-methyl-benzoic acid reacted N-bromosuccinimide, then with chlorohydric acid, and last with caprolactam to produce 4-chloromethyl benzoyl caprolactam. N, N, N-triethyl-4[(hexahydro-2-oxo-1H-azepin-1-yl)carbonyl]-, Chloride(TBCC) was further synthesized via the reaction with triethylamine and 4-chloromethyl benzoyl. The total yield was 40.8%. The molecular structures of fifteen products were characterized by 1H NMR and measuring melting-point, and the compounds obtained was final objective products. A new technology to synthesis of TBCC/TBCB was put forward. This method was of characteristic of high yield, the widely sources of raw material, safe operation, low cost and so on. PartⅡ:In the thesis, the synthesis of Imatinib was from nicotinic acid, 2-amino-4-nitro-toluene and 4-methyl-benzoic acid. And we do further research on the synthesis of some intermediates. The yield of 4-(4-methyl-piperazinyl) benzoic acid is 63.0%; The yield of 3-(3-(dimethylamino) allyl carbonyl) pyridine is 68.0%; The yield of N-(5-amino-2-methyl-phenyl)-4-(3-pyridyl)-2-piperidine amine is 82.8%.The route was characterized by feasible materials, higher yield and milder conditions. The products were all solid, so It was very easy for purification and it was apposite for the industrialization.The structure of the compounds were all characterized by 1H NMR.The results showed that the structures of the compounds in accordance with the requirement. This predicted that the route was feasible.