新产品编号:653875
Chemical Name: (-)-2,6-Dimethyl-5-nitro-4(S)-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylic acid 2-(nitrooxy)ethyl ester
CAS No. 250330-33-7, 250330-34-8 (enantiomer), 339528-66-4 (undefined stereochem.)
项目整合开发状态: Biological Testing
项目研究机构: Dalhousie University (Originator), University of Alberta (Originator)
合成路线:D-Threonine (I) was esterified by means of thionyl chloride in methanol,and the resultant amino ester (II) was subsequently acylated with 3,5-dinitrobenzoyl chloride (III) to afford amide (IV).Conversion of (IV) to the acetoacetate ester (VI) was effected by reaction with the diketene precursor 2,2,6-trimethyl-4H-1,3-dioxin-4-one (V) in boiling xylene.Treatment of keto ester (V) with ammonia in the presence of p-toluenesulfonic acid produced the aminocrotonate ester (VI).Dihydropyridine (IXa-b) was then obtained as a diastereomeric mixture by a modified Hantzsh condensation between enamine (VI),2-trifluoromethylbenzaldehyde (VII) and nitroacetone.After chromatographic separation of the isomers,the chiral auxiliary group was removed by methanolysis in the presence of DBU.The desired (+)-(S)-dihydropyridinecarboxylic acid (X) was finally converted to the nitrooxyethyl ester by reaction with 2-bromoethyl nitrate (XI).
📌 参考资料/链接：
参考文献标题:The design of (-)-(S)-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate: A cardioselective positive inotropic derivative of Bay K 8644
文献作者:Shan,R.; Knaus,E.E.
参考来源:Bioorg Med Chem Lett 1999,9(17),2613
📄 详细内容
合成路线:D-Threonine (I) was esterified by means of thionyl chloride in methanol,and the resultant amino ester (II) was subsequently acylated with 3,5-dinitrobenzoyl chloride (III) to afford amide (IV).Conversion of (IV) to the acetoacetate ester (VI) was effected by reaction with the diketene precursor 2,2,6-trimethyl-4H-1,3-dioxin-4-one (V) in boiling xylene.Treatment of keto ester (V) with ammonia in the presence of p-toluenesulfonic acid produced the aminocrotonate ester (VI).Dihydropyridine (IXa-b) was then obtained as a diastereomeric mixture by a modified Hantzsh condensation between enamine (VI),2-trifluoromethylbenzaldehyde (VII) and nitroacetone.After chromatographic separation of the isomers,the chiral auxiliary group was removed by methanolysis in the presence of DBU.The desired (+)-(S)-dihydropyridinecarboxylic acid (X) was finally converted to the nitrooxyethyl ester by reaction with 2-bromoethyl nitrate (XI).
参考文献标题:Syntheses,calcium channel agonist-antagonist modulation activities,nitric oxide release,and voltage-clamp studies of 2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate enantiomers
文献作者:Shan,R.; Howlett,S.E.; Knaus,E.E.
参考来源:J Med Chem 2002,45(4),955