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【结 构 式】 
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【分子编号】27639 【品名】isobutyl 2-[(3R,5S)-3-(4-cyanophenyl)-2-methylisoxazolidinyl]acetate 【CA登记号】 |
【 分 子 式 】C17H22N2O3 【 分 子 量 】302.37336 【元素组成】C 67.53% H 7.33% N 9.26% O 15.87% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 4-formylbenzonitrile (I) with N-methylhyddroxylamine (II) by means of Na2CO3 in dichloromethane gives the nitrone (III), which is cyclized with isobutyl 3-butenoate (IV) by heating at 100 C to afford the cis-isoxazolidinyl acetate (V) (along with some trans isomer) that is purified by chromatography. The hydrolysis of the ester (V) with LiOH in THF/water yields the free acid (VI), which is condensed with the diamino ester (VII) by means of PyBop and Et3N in DMF giving the intermediate (VIII). The treatment of (VII) with dry HCl in methanol/chloroform to convert the CN group into amidino yields derivative (IX), which is finally hydrolyzed to the free acid with aqueous HCl.
| 【1】 Confalone, P.N.; Jin, F.; Mousa, S.A.; Platelet glycoprotein IIb/IIIa receptor antagonists derived from isoxazolidines. Bioorg Med Chem Lett 1999, 9, 1, 55. |
| 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) | 17552 | 4-formylbenzonitrile; 4-Cyanobenzaldehyde | 105-07-7 | C8H5NO | 详情 | 详情 |
| (II) | 12690 | (Hydroxyamino)methane; N-Methylhydroxylamine | 593-77-1 | CH5NO | 详情 | 详情 |
| (III) | 27637 | 4-[[methyl(oxo)-lambda(5)-azanylidene]methyl]benzonitrile | C9H8N2O | 详情 | 详情 | |
| (IV) | 27638 | isobutyl 3-butenoate | 24342-03-8 | C8H14O2 | 详情 | 详情 |
| (V) | 27639 | isobutyl 2-[(3R,5S)-3-(4-cyanophenyl)-2-methylisoxazolidinyl]acetate | C17H22N2O3 | 详情 | 详情 | |
| (VI) | 27640 | 2-[(3R,5S)-3-(4-cyanophenyl)-2-methylisoxazolidinyl]acetic acid | C13H14N2O3 | 详情 | 详情 | |
| (VII) | 25970 | methyl (2S)-3-amino-2-[(phenylsulfonyl)amino]propanoate | C10H14N2O4S | 详情 | 详情 | |
| (VIII) | 27641 | methyl (2S)-3-([2-[(3R,5S)-3-(4-cyanophenyl)-2-methylisoxazolidinyl]acetyl]amino)-2-[[(4-methyl-2-pyridinyl)sulfonyl]amino]propanoate | C23H27N5O6S | 详情 | 详情 | |
| (IX) | 27642 | methyl (2S)-3-[[2-((3R,5S)-3-[4-[amino(imino)methyl]phenyl]-2-methylisoxazolidinyl)acetyl]amino]-2-[[(3-methylphenyl)sulfonyl]amino]propanoate | C24H31N5O6S | 详情 | 详情 |