|
【结 构 式】 
|
【分子编号】18009 【品名】tert-butyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate 【CA登记号】 |
【 分 子 式 】C15H22N2O4 【 分 子 量 】294.35076 【元素组成】C 61.21% H 7.53% N 9.52% O 21.74% |
合成路线1
该中间体在本合成路线中的序号：(III)Treatment of amino acid (I) with isobutylene (II) and H2SO4 in dioxane afforded tert-butyl ester (III), which was coupled with carboxylic acid (IV) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and 1-hydroxybenzotriazole (HOBT) to give (V). Removal of the benzyloxycarbonyl protecting group by hydrogenolysis provided amine (VI) which, on reaction with 2-bromotoluenesulfonyl chloride (VII) and pyridine in refluxing ethyl acetate was converted into sulfonamide (VIII). Deprotection of both tert-butyl groups was effected by treatment with trifluoroacetic acid in dichloromethane, to give (IX) as the trifluoroacetate salt. Tritium labeled compound was then obtained by reductive debromination with tritium gas, using Pearlman's catalyst in the presence of triethylamine.
| 【1】 Thorell, J.O.; et al.; Synthesis of a C-11-labelled nitrated 1,4-dihydroquinoxaline-2,3-dione, the NMDA glycine receptor antagonist ACEA 1021 (Licostinel). J Label Compd Radiopharm 1998, 41, 4, 345-353. |
| 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) | 18008 | (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid | 35761-26-3 | C11H14N2O4 | 详情 | 详情 |
| (II) | 15926 | 2-methyl-1-propene; isobutylene | 115-11-7 | C4H8 | 详情 | 详情 |
| (III) | 18009 | tert-butyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate | C15H22N2O4 | 详情 | 详情 | |
| (IV) | 18010 | 5-[2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl]-4-oxo-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxylic acid | C20H30N4O5 | 详情 | 详情 | |
| (V) | 18011 | tert-butyl 4-[2-[2-([[(2S)-2-[[(benzyloxy)carbonyl]amino]-3-(tert-butoxy)-3-oxopropyl]amino]carbonyl)-4-oxo-7,8-dihydro-4H-pyrazolo[1,5-a][1,4]diazepin-5(6H)-yl]ethyl]-1-piperidinecarboxylate | C35H50N6O8 | 详情 | 详情 | |
| (VI) | 18012 | tert-butyl 4-[2-[2-([[(2S)-2-amino-3-(tert-butoxy)-3-oxopropyl]amino]carbonyl)-4-oxo-7,8-dihydro-4H-pyrazolo[1,5-a][1,4]diazepin-5(6H)-yl]ethyl]-1-piperidinecarboxylate | C27H44N6O6 | 详情 | 详情 | |
| (VII) | 18013 | 2-bromo-4-methylbenzenesulfonyl chloride | C7H6BrClO2S | 详情 | 详情 | |
| (VIII) | 18014 | tert-butyl 4-[2-[2-([[(2S)-2-[[(2-bromo-4-methylphenyl)sulfonyl]amino]-3-(tert-butoxy)-3-oxopropyl]amino]carbonyl)-4-oxo-7,8-dihydro-4H-pyrazolo[1,5-a][1,4]diazepin-5(6H)-yl]ethyl]-1-piperidinecarboxylate | C34H49BrN6O8S | 详情 | 详情 | |
| (IX) | 18015 | (2S)-2-[[(2-bromo-4-methylphenyl)sulfonyl]amino]-3-[([4-oxo-5-[2-(4-piperidinyl)ethyl]-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carbonyl)amino]propionic acid | C25H33BrN6O6S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Conversion of amino acid (I) into its methyl ester derivative (II) by means of SOCl2 in MeOH, followed by coupling with ethyl isocyanatoacetate (III) and Et3N in CH2Cl2/THF yields derivative (IV). Cyclization of (IV) by means of H2O/HCl affords hydantoin (V), which reacts with 2-methylthio-2-imidazoline (VI) in an aqueous NaOH solution to provide cyclic guanidine derivative (VII). Treatment of amino acid (VIII) with isobutylene (IX) and H2SO4 in dioxane affords t-Bu ester (X), which then couples with (VII) by means of HOBt and DCC in DMF to furnish derivative (XI). Finally, tert-butyl ester is hydrolyzed by treatment with TFA in the presence of 1,2-dimercaptoethane.
| 【1】 Knolle, J.; Peyman, A.; Wehner, V.; et al.; RGD mimetics containing a central hydantoin scaffold: alphavbeta3 vs alphaIIbbeta3 selective requirements. Bioorg Med Chem Lett 2000, 10, 2, 179. |
| 【2】 Wehner, V.; Knolle, J.; Stilz, H.U.; Carniato, D.; Gourvest, J.-F.; Gadek, T.; McDowell, R. (Aventis SA); Inhibitors of bone resorption and vitronectin receptor antagonists. DE 19626701; DE 19635522; EP 0796855 . |
| 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) | 30898 | (2S)-2-amino-5-[[(benzyloxy)carbonyl]amino]pentanoic acid | C13H18N2O4 | 详情 | 详情 | |
| (II) | 42993 | methyl (2S)-2-amino-5-[[(benzyloxy)carbonyl]amino]pentanoate | C14H20N2O4 | 详情 | 详情 | |
| (III) | 18312 | ETHYL ISOCYANATOACETATE; ethyl 2-isocyanatoacetate | 2949-22-6 | C5H7NO3 | 详情 | 详情 |
| (IV) | 42994 | 12-ethyl 8-methyl (8S)-3,10-dioxo-1-phenyl-2-oxa-4,9,11-triazadodecane-8,12-dicarboxylate | C19H27N3O7 | 详情 | 详情 | |
| (V) | 42295 | (2R)-N-methyl-2-(methylamino)-3-(2-naphthyl)-N-[(1R)-2-oxo-1-(2-thienylmethyl)-2-(1,2,2-trimethylhydrazino)ethyl]propanamide | C25H32N4O2S | 详情 | 详情 | |
| (VI) | 42996 | 4,5-dihydro-1H-imidazol-2-yl methyl sulfide; 2-(methylsulfanyl)-4,5-dihydro-1H-imidazole | 5464-11-9 | C4H8N2S | 详情 | 详情 |
| (VII) | 42997 | 2-[(4S)-4-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]-2,5-dioxoimidazolidinyl]acetic acid | C11H17N5O4 | 详情 | 详情 | |
| (VIII) | 18008 | (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid | 35761-26-3 | C11H14N2O4 | 详情 | 详情 |
| (IX) | 15926 | 2-methyl-1-propene; isobutylene | 115-11-7 | C4H8 | 详情 | 详情 |
| (X) | 18009 | tert-butyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate | C15H22N2O4 | 详情 | 详情 | |
| (XI) | 42998 | tert-butyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[(2-[(4S)-4-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]-2,5-dioxoimidazolidinyl]acetyl)amino]propanoate | C26H37N7O7 | 详情 | 详情 |