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【结 构 式】 
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【分子编号】22480 【品名】tert-butyl 2-[(1-[(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]-4-piperidinyl)oxy]acetate 【CA登记号】 |
【 分 子 式 】C24H38N2O5 【 分 子 量 】434.5762 【元素组成】C 66.33% H 8.81% N 6.45% O 18.41% |
合成路线1
该中间体在本合成路线中的序号：(IX)The acylation of 4-hydroxypiperidine (I) with benzyl chloroformate (II) by means of triethylamine in dichloromethane gives 4-hydroxypiperidine-1-carboxylic acid benzyl ester (III), which is condensed with tert-butyl bromoacetate (IV) by means of tetrabutylammonium hydrogensulfate and NaOH in toluene/water, affording 2-[1-(benzyloxycarbonyl)piperidin-4-yloxy]acetic acid tert-butyl ester (V). The deprotection of (V) by hydrogenation with H2 over Pd/C in ethanol gives the piperidine (VI), which is condensed with N-(benzyloxycarbonyl)-4-O-tert-butyl-L-tyrosine (VII) by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) in dichloromethane, yielding the expected condensation product (VIII). The deprotection of the amino group of (VIII) by hydrogenation as before affords (IX), which is N-acylated with 4-amidinobenzoyl chloride (X), prepared by reaction of 4-amidinobenzoic acid (XI) with SOCl2, giving the bis-tert-butylated product (XII). Finally, this compound is deprotected by means of trifluoroacetic acid in dichloromethane.
| 【1】 Weller, T.; Hadvary, P.; Trzeciak, A.; Knopp, D.; Steiner, B.; Edenhofer, A.; Muller, M.; Hurzeler, M.; Alig, L.; Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 1992, 35, 23, 4393. |
| 【2】 Castaner, J.; Merlos, M.; Cases, A.; Rabasseda, X.; Lamifiban. Drugs Fut 1999, 24, 3, 261. |
| 【3】 Alig, L.; Hadvary, P.; Huzeler, M.; Muller, M.; Steiner, B.; Weller, T. (F. Hoffmann-La Roche AG); N-acyl-alpha-aminoacids derivs.. EP 0505868; JP 1993148204; US 5378712; US 5545658; US 5658928; US 5670515; US 5747522 . |
| 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) | 12076 | 4-Piperidinol; 4-Hydroxypiperidine | 5382-16-1 | C5H11NO | 详情 | 详情 |
| (II) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (III) | 19284 | benzyl 4-hydroxy-1-piperidinecarboxylate | C13H17NO3 | 详情 | 详情 | |
| (IV) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (V) | 19286 | benzyl 4-[2-(tert-butoxy)-2-oxoethoxy]-1-piperidinecarboxylate | C19H27NO5 | 详情 | 详情 | |
| (VI) | 19287 | tert-butyl 2-(4-piperidinyloxy)acetate | C11H21NO3 | 详情 | 详情 | |
| (VII) | 22478 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(tert-butoxy)phenyl]propionic acid | C21H25NO5 | 详情 | 详情 | |
| (VIII) | 22479 | tert-butyl 2-[(1-[(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(tert-butoxy)phenyl]propanoyl]-4-piperidinyl)oxy]acetate | C32H44N2O7 | 详情 | 详情 | |
| (IX) | 22480 | tert-butyl 2-[(1-[(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]-4-piperidinyl)oxy]acetate | C24H38N2O5 | 详情 | 详情 | |
| (X) | 22481 | 4-[amino(imino)methyl]benzoyl chloride | C8H7ClN2O | 详情 | 详情 | |
| (XI) | 22482 | 4-Amidinobenzic acid; 4-[amino(imino)methyl]benzoic acid | 15535-95-2 | C8H8N2O2 | 详情 | 详情 |
| (XII) | 22483 | tert-butyl 2-[(1-[(2S)-2-([4-[amino(imino)methyl]benzoyl]amino)-3-[4-(tert-butoxy)phenyl]propanoyl]-4-piperidinyl)oxy]acetate | C32H44N4O6 | 详情 | 详情 |