E-3174, EXP-3174

氯沙坦Chemical Name: 2-Butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid
CAS No. 124750-92-1
项目整合开发状态: Phase III
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Synthesis of imidazole (V) first entails the conversion of valeronitrile (I) to its imidate ester (II).Subsequent reaction with 1,3-dihydroxyacetone dimer and ammonia leads to imidazole (III).Chlorination with N-chlorosuccinimide yields the 4-chloroimidazole (IV).Oxidation with manganese dioxide finally yields imidazole-5-carboxaldehyde (V).

合成路线:The synthesis of the biphenyl tail involves first the conversion of 2-methoxybenzoic acid (VI) into oxazoline (VII),followed by displacement of the methoxy group by 4-tolylmagnesium bromide to yield biphenyloxazoline (VIII).Oxazoline (VIII) may be converted into biphenylnitrile (IX) by reaction with phosphorous oxychloride in pyridine.Reaction of biphenylnitrile (VIII) with tri-n-butyltin azide in refluxing xylenes,followed by destannylation and protection with a triphenylmethyl group,yields triphenylmethyl-protected biphenyltetrazole (X).Benzylic bromination yields the completed tail (XI)

合成路线:The compound is assembled by connecting the imidazole head (V) to the biphenyltetrazole tail (XI).The aldehyde (V) undergoes regioselective alkylation with bromide (XI).Subsequent reduction of the aldehyde group in the same pot yields adduct (XII).Deprotection in acid,followed by conversion to the potassium salt,yields DuP-753.

合成路线:EXP3174 is obtained from DuP 753 (Entry Number: 162288).