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【结 构 式】

【药物名称】

【化学名称】3(S)-(3-Fluorophenyl)-3-[2-[2-oxo-3(S)-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]acetamido]propionic acid

【CA登记号】

【 分 子 式 】C25H29FN4O4

【 分 子 量 】468.53268

【开发单位】Merck & Co. (Originator)

【药理作用】Bone Diseases, Treatment of, METABOLIC DRUGS, Treatment of Osteoporosis, Integrin alphavbeta3 (Vitronectin) Antagonists

合成路线1

Ethyl 3-fluorocinnamate (III) was prepared by Wittig condensation of 3-fluorobenzaldehyde (I) with phosphorane (II). Conjugate addition of (R)-N-benzyl-alpha-methylbenzylamine (IV) to the unsaturated ester (III) furnished the chiral amino ester (V). The primary amine (VI) was then obtained by hydrogenolysis of the N-benzyl groups in the presence of palladium hydroxyde. Coupling of the known pyrrolidinoneacetic acid (VII) to the amino ester (VI) by means of EDC/HOBt afforded amide (VIII). Finally, saponification of the ethyl ester group of (VIII) led to the corresponding carboxylic acid.

1 Brashear, K.M.; Hunt, C.A.; Coleman, P.J.; et al.; Non-peptide alphavbeta3 antagonists. Part 3: Identification of potent RGD mimetics incorporating novel beta-amino acids as aspartic acid replacements. Bioorg Med Chem Lett 2002, 12, 1, 31.
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) 18887 3-Fluorobenzaldehyde 456-48-4 C7H5FO 详情 详情
(II) 14182 ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane 1099-45-2 C22H21O2P 详情 详情
(III) 59701 Ethyl (E)-3-(3-fluorophenyl)-2-propenoate; Ethyl 3-fluorocinnamate C11H11FO2 详情 详情
(IV) 47881 (1R)-N-benzyl-1-phenyl-1-ethanamine; N-benzyl-N-[(1R)-1-phenylethyl]amine C15H17N 详情 详情
(V) 59702 ethyl (3S)-3-{benzyl[(1R)-1-phenylethyl]amino}-3-(3-fluorophenyl)propanoate C26H28FNO2 详情 详情
(VI) 59703 ethyl (3S)-3-amino-3-(3-fluorophenyl)propanoate C11H14FNO2 详情 详情
(VII) 59704 2-{(3S)-2-oxo-3-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethyl]pyrrolidinyl}acetic acid C16H21N3O3 详情 详情
(VIII) 59705 ethyl (3S)-3-(3-fluorophenyl)-3-[(2-{(3S)-2-oxo-3-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethyl]pyrrolidinyl}acetyl)amino]propanoate C27H33FN4O4 详情 详情
Extended Information