【结 构 式】 |
【分子编号】48287 【品名】(2S)-2-(2-benzoylanilino)-N-[1-(hydroxymethyl)-2-methylpropyl]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide 【CA登记号】 |
【 分 子 式 】C39H41N3O5 【 分 子 量 】631.77176 【元素组成】C 74.15% H 6.54% N 6.65% O 12.66% |
合成路线1
该中间体在本合成路线中的序号:(VII)Condensation of L-tyrosine methyl ester (I) with 2-benzoylcylohexanone (II) and subsequent dehydrogenation in refluxing anisole in the presence of Pd/C affords the benzophenone derivative (III), which is converted into carboxylic acid (V) by Mitsunobu reaction with heterocyclic alcohol (IV) by means of PPh3 and DEAD in THF followed by saponification of the resulting methyl ester with LiOH in THF/MeOH (1). Coupling of (V) with valinol (VI) by means of HOBt/Et3N and EDC·HCl in CH2Cl2 furnishes amide (VII), which is oxidized by means of 4-methylmorpholine (NMM) and TPAP in CH2Cl2 to furnish aldehyde (VIII). Finally, the desired oxazole is obtained by intramolecular cyclization of (VIII) by means of iodine, PPh3 and Et3N in CH2Cl2.
【1】 N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel serieis of potent antihyperglycemic and antihyperlipidemic agents. J Med Chem 1998, 41, 25, 5020. |
【2】 Cobb, J.E.; Shearer, B.G.; Lambert, M.H. III; Milburn, M.V. (Glaxo Group Ltd.); Oxazole PPAR antagonists. WO 0117994 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 21431 | methyl (2S)-2-amino-3-(4-hydroxyphenyl)propanoate | 1080-06-4 | C10H13NO3 | 详情 | 详情 |
(II) | 21432 | 2-benzoylcyclohexanone | 3580-38-9 | C13H14O2 | 详情 | 详情 |
(III) | 21434 | methyl (2S)-2-(2-benzoylanilino)-3-(4-hydroxyphenyl)propanoate | C23H21NO4 | 详情 | 详情 | |
(IV) | 19874 | 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-1-ethanol | C12H13NO2 | 详情 | 详情 | |
(V) | 48285 | (2S)-2-(2-benzoylanilino)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propionic acid | C34H30N2O5 | 详情 | 详情 | |
(VI) | 48289 | 2-amino-3-methyl-1-butanol; DL-Valinol | 473-75-6 | C5H13NO | 详情 | 详情 |
(VII) | 48287 | (2S)-2-(2-benzoylanilino)-N-[1-(hydroxymethyl)-2-methylpropyl]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide | C39H41N3O5 | 详情 | 详情 | |
(VIII) | 48288 | (2S)-2-(2-benzoylanilino)-N-(1-formyl-2-methylpropyl)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanamide | C39H39N3O5 | 详情 | 详情 |