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【结 构 式】 
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【分子编号】54770 【品名】methyl 3-{[2-({4-[(4-methyl-2-pyridinyl)amino]butanoyl}amino)acetyl]amino}-3-[4-(1-naphthyl)phenyl]propanoate 【CA登记号】 |
【 分 子 式 】C32H34N4O4 【 分 子 量 】538.64652 【元素组成】C 71.36% H 6.36% N 10.4% O 11.88% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The 3-aryl-3-aminopropionic acid (II) was prepared by Knoevenagel condensation of 4-(1-naphthyl)benzaldehyde (I) with malonic acid in the presence of ammonium acetate. Subsequent esterification of (II) by means of thionyl chloride and methanol afforded the methyl ester (III). Coupling of amino ester (III) with N-Boc-glycine (IV) by means of TBTU and HOBt furnished amide (V). After acidic Boc group cleavage, the resultant dipeptide ester (VI) was acylated with 4-(4-methylpyridin-2-ylamino)butyric acid (VII), yielding tripeptide ester (VIII). The methyl ester group of (VIII) was finally hydrolyzed by NaOH in aqueous dioxan.
| 【1】 Goodman, S.L.; Holzemann, G.; Kessler, H.; Sulyok, G.A.G.; Nanomolar small molecule inhibitors for alphavbeta6, alphavbeta5, and +alphavbeta3 integrins. J Med Chem 2002, 45, 5, 1045. |
| 【2】 Holzemann, G.; Jonczyk, A.; Goodman, S.; Stahle, W. (Merck Patent GmbH); beta-Alanine derivs.. WO 0048996 . |
| 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) | 54764 | 4-(1-naphthyl)benzaldehyde | C17H12O | 详情 | 详情 | |
| (II) | 54765 | 3-[4-(1-naphthyl)phenyl]-beta-alanine | C19H17NO2 | 详情 | 详情 | |
| (III) | 54766 | methyl 3-amino-3-[4-(1-naphthyl)phenyl]propanoate | C20H19NO2 | 详情 | 详情 | |
| (IV) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (V) | 54767 | methyl 3-({2-[(tert-butoxycarbonyl)amino]acetyl}amino)-3-[4-(1-naphthyl)phenyl]propanoate | C27H30N2O5 | 详情 | 详情 | |
| (VI) | 54768 | methyl 3-[(2-aminoacetyl)amino]-3-[4-(1-naphthyl)phenyl]propanoate | C22H22N2O3 | 详情 | 详情 | |
| (VII) | 54769 | 4-[(4-methyl-2-pyridinyl)amino]butanoic acid | C10H14N2O2 | 详情 | 详情 | |
| (VIII) | 54770 | methyl 3-{[2-({4-[(4-methyl-2-pyridinyl)amino]butanoyl}amino)acetyl]amino}-3-[4-(1-naphthyl)phenyl]propanoate | C32H34N4O4 | 详情 | 详情 |