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【结 构 式】 
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【分子编号】28336 【品名】tert-butyl (1R)-2-amino-1-benzyl-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C14H20N2O3 【 分 子 量 】264.32448 【元素组成】C 63.62% H 7.63% N 10.6% O 18.16% |
合成路线1
该中间体在本合成路线中的序号：(XVI)The reaction of 3,3-dimethylglutaric acid monomethyl ester (XI) with SOCl2 in dichloromethane gives the monoacyl chloride (XII), which is condensed with thiophene (III), by means of SnCl4 in dichloromethane yielding the 5-oxopentanoic ester (XIII). The reduction and simultaneous hydrolysis of (XIII) with hydrazine and KOH affords the pentanoic acid (XIV), which is reesterified with ethanol and sulfuric acid to the ester (XV). The condensation of (XV) with the previously described 3-phenylpropionyl chloride (II) by means of SnCl4 in dichloromethane gives the propanone derivative (XVI), which is reduced with hydrazine and KOH to the previously described pentanoic acid (VIII). Its condensation with piperazine (IX) to afford (X) and the final reduction to the target compound have already been described.
| 【1】 Wierzbicki, M.; et al.; Amino derivatives of phenyl alkyl thiophene as inhibitors of bone resorption. Structure-activity relationship. Arzneim-Forsch Drug Res 1998, 48, 8, 840. |
| 【2】 Wierzbicki, M.; Sauveur, F.; Bonnet, J.; Brisset, M.; Tordjman, C. (ADIR et Cie.); Thiophene derivs., process for their preparation and pharmaceutical compsns. containing them. AU 9166901; EP 0429370; FR 2655043; JP 1991190872; US 5061704 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 28329 | 3-(4-methylphenyl)propanoyl chloride | C10H11ClO | 详情 | 详情 | |
| (III) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (VIII) | 28333 | 3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]pentanoic acid | C21H28O2S | 详情 | 详情 | |
| (IX) | 24354 | 2,3-dimethoxy-4-(1-piperazinylmethyl)phenyl methyl ether | C14H22N2O3 | 详情 | 详情 | |
| (X) | 28334 | 3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-1-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]-1-pentanone | C35H48N2O4S | 详情 | 详情 | |
| (XI) | 28322 | 5-methoxy-3,3-dimethyl-5-oxopentanoic acid | C8H14O4 | 详情 | 详情 | |
| (XII) | 28323 | methyl 5-chloro-3,3-dimethyl-5-oxopentanoate | C8H13ClO3 | 详情 | 详情 | |
| (XIII) | 28324 | methyl 3,3-dimethyl-5-oxo-5-(2-thienyl)pentanoate | C12H16O3S | 详情 | 详情 | |
| (XIV) | 28325 | 3,3-dimethyl-5-(2-thienyl)pentanoic acid | C11H16O2S | 详情 | 详情 | |
| (XV) | 28326 | ethyl 3,3-dimethyl-5-(2-thienyl)pentanoate | C13H20O2S | 详情 | 详情 | |
| (XVI) | 28336 | tert-butyl (1R)-2-amino-1-benzyl-2-oxoethylcarbamate | C14H20N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)This peptide has been obtained by by the usual method of solid phase resin starting from N-Boc-protected D-phenylalanine coupled to a methylbenzhydryl amine polystyrene resin (I) by successive cycles of Boc deprotection and coupling. The amino acid used were successively, N-Boc-D-tryptophan (II), N-Boc-D-arginine (IV), N-Boc-D-isoleucine (VI), N-Boc-D-phenylalanine (VIII) and N-Boc-D-histidine (X), yielding the intermediate peptide-resins (III), (V), (VII), (IX), and (XI). Finally, this last intermediate was deprotected and cleaved from the resin with HF, acetylated at the N-terminus and amidated at the C-terminus using standard methods.
| 【1】 Baumbach, W.R.; Carrick, T.A.; Pausch, M.H.; Bingham, B.; Carmignac, D.; Robinson, I.C.A.F.; Houghten, R.; Eppler, C.M.; Price, L.A.; Zysk, J.R.; A linear hexapeptide somatostatin antagonist blocks somatostatin activity in vitro and influences growth hormone release in rats. Mol Pharmacol 1998, 54, 5, 864. |
| 【2】 Houghten, R.A.; Baumbach, W.R. (American Cyanamid Co.); Peptides useful as somatostatin antagonists. EP 0863156 . |
| 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) | 28336 | tert-butyl (1R)-2-amino-1-benzyl-2-oxoethylcarbamate | C14H20N2O3 | 详情 | 详情 | |
| (II) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (III) | 28337 | tert-butyl (1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate | C25H30N4O4 | 详情 | 详情 | |
| (IV) | 28344 | (2R)-5-[[amino(imino)methyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | C11H22N4O4 | 详情 | 详情 | |
| (V) | 28338 | tert-butyl (1R)-1-([[(1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-4-[[amino(imino)methyl]amino]butylcarbamate | C31H42N8O5 | 详情 | 详情 | |
| (VI) | 28339 | (2R,3R)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | C11H21NO4 | 详情 | 详情 | |
| (VII) | 28340 | tert-butyl (1R,2R)-1-[[((1R)-1-([[(1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-4-[[amino(imino)methyl]amino]butyl)amino]carbonyl]-2-methylbutylcarbamate | C37H53N9O6 | 详情 | 详情 | |
| (VIII) | 22184 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid | C14H19NO4 | 详情 | 详情 | |
| (IX) | 28341 | tert-butyl (1R,4R,7R,10R,13R)-14-amino-7-(3-[[amino(imino)methyl]amino]propyl)-1,13-dibenzyl-10-(1H-indol-3-ylmethyl)-4-[(1R)-1-methylpropyl]-2,5,8,11,14-pentaoxo-3,6,9,12-tetraazatetradec-1-ylcarbamate | C46H62N10O7 | 详情 | 详情 | |
| (X) | 28342 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid | 50654-94-9 | C11H17N3O4 | 详情 | 详情 |
| (XI) | 28343 | tert-butyl (1R,4R,7R,10R,13R,16R)-17-amino-10-(3-[[amino(imino)methyl]amino]propyl)-4,16-dibenzyl-1-(1H-imidazol-5-ylmethyl)-13-(1H-indol-3-ylmethyl)-7-[(1R)-1-methylpropyl]-2,5,8,11,14,17-hexaoxo-3,6,9,12,15-pentaazaheptadec-1-ylcarbamate | C52H69N13O8 | 详情 | 详情 |