The Synthesize Research Of Candesartan

Candesartan scientific name2-ethoxy-1-[[2’-(1H-tetraza thiazolyl-5)biphenyl-4-]methyl]benzimidazole-7-carboxylic acid, is an antihypertensive drug. Acting on the renin-angiotensin-aldosterone system has good specificity selectivity, fewer adverse reactions, lasting effect and longhalf-life and other superior characteristics. Candesartan market has great potential and broadprospects. Therefore, the study of Candesartan improve the yield of the synthesis process has important significance.After analysis and comparison, Kobe Takehiko Naka Synthesis process route. Phthalic anhydride as the starting material,3-nitro-phthalate(1)by nitration,3-nitro-phthalate obtained byalcohol esterification of3-nitro-2-carboxyl acid ethyl ester (2),3-nitro-2-carboxy benzoate obtained by thionyl chloride to give3-nitro-2-chlorideyl benzoate(3),3-nitro-2-chlorideyl benzoate by sodium azide and tert-butanol, the Curtius rearrangement to give3-nitro-2-t-butoxy-formamido-benzoate acid ethyl ester (5),3-nitro-2-t-butoxy-formamido-benzoate was bromobiphenyl the N-hydrocarbyl obtained2-[[(2＇cyanobiphenyl-4-yl)methyl-amino]-3-nitrophenyl ethyl(6),2-[(2＇cyanobiphenyl-4-yl)methyl]amino]-3-nitrobenzoate(6) by stannous chloride reducingthe nitro group to give2-[(2＇cyanobiphenyl-4-yl)methyl]amino]-3-amino-benzoic acid ethyl ester(7),2-[(2＇cyano-biphenyl-4-yl)methyl-amino]-3-amino-benzoic acid ethyl ester(8) cyclization2-ethoxy-1-[(2＇cyano-biphenyl-4-yl)methyl]benzimidazole-7-carboxylic acid ethyl ester hydrochloride under the conditions of the sodium azide/triethylamine cyclization then hydrolyzed to give the final product candesartan. Determined by orthogonal experiments the optimum reaction conditions for each step, the total yield of (phthalic anhydride dollars) reached10.3%, higher than the offering yield of9.3%The structure of all intermediates and final products were confirmed by nuclearmagnetic resonance spectroscopy, infrared spectroscopy.