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【结 构 式】

【分子编号】23627

【品名】(2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid

【CA登记号】

【 分 子 式 】C14H18N2O4

【 分 子 量 】278.308

【元素组成】C 60.42% H 6.52% N 10.07% O 23%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IX)

N-Boc-Homophenylalanine (I) was coupled to N,O-dimethyl hydroxylamine using DCC, and the resulting N-methoxy amide (II) was reduced to aldehyde (III) with LiAlH4. Sulfonyl phosphonate (VI), (prepared from methyl phenyl sulfone (IV) and diethyl chlorophosphate (V)), was then condensed with aldehyde (III) in the presence of NaH to provide the vinylogous sulfone (VII). Subsequent acid deprotection of the Boc group of (VII) yielded amine (VIII). This was finally coupled with mixed anhydride (X), (obtained from morpholinocarbonyl-phenylalanine (IX) and isobutyl chloroformate in the presence of N-methylmorpholine), to furnish the target amide.

1 Rasnick, D.; Klaus, J.L.; Palmer, J.T. (Khepri Pharmaceuticals Inc.); Irreversible cysteine protease inhibitors containi. WO 9523222 .
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) 23619 (2S)-2-[(tert-butoxycarbonyl)amino]-4-phenylbutyric acid 100564-78-1 C15H21NO4 详情 详情
(II) 23620 tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-phenylpropylcarbamate C17H26N2O4 详情 详情
(III) 23621 tert-butyl (1S)-1-formyl-3-phenylpropylcarbamate C15H21NO3 详情 详情
(IV) 23622 methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane 3112-85-4 C7H8O2S 详情 详情
(V) 23623 Chlorophosphoric acid ethyl ester;Phosphorochloridic acid diethyl ester;Diethyl chlorophosphate;diethyl phosphorochloridate 814-49-3 C4H10ClO3P 详情 详情
(VI) 23624 diethyl (phenylsulfonyl)methylphosphonate C11H17O5PS 详情 详情
(VII) 23625 tert-butyl (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylcarbamate C22H27NO4S 详情 详情
(VIII) 23626 (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylamine; (E,3S)-5-phenyl-1-(phenylsulfonyl)-1-penten-3-amine C17H19NO2S 详情 详情
(IX) 23627 (2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid C14H18N2O4 详情 详情
(X) 23628 N-(4-Morpholinylcarbonyl)-L-phenylalanine ethoxycarbonyl anhydride C17H22N2O6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

The Horner-Wadsworth-Emmons olefination of N-(tert-butoxycarbonyl)-L-homophenylalaninal (I) with phosphonate (II) by means of NaH in THF gives the vinylsulfonate (III), which is treated with tetrabutylammonium iodide and triphosgene to yield the sulfonyl chloride (IV). The reaction of (IV) with O-benzylhydroxylamine in dichloromethane affords the N-sulfonylhydroxylamine derivative (V), which is deprotected with TFA in dichloromethane, providing compound (VI) with a free amino group. Finally, this compound is condensed with N-(morpholin-4-ylcarbonyl)-L-phenylalanine (VII) by means of HOBt, EDC and NMM in DMF, giving rise to the target amide.

1 Roush, W.R.; et al.; Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg Med Chem Lett 2001, 11, 20, 2759.
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) 23624 diethyl (phenylsulfonyl)methylphosphonate C11H17O5PS 详情 详情
(II) 51650 ethyl dimethoxy(oxo)phosphoranesulfonate C4H11O6PS 详情 详情
(III) 51651 ethyl (E,3S)-3-[(tert-butoxycarbonyl)amino]-5-phenyl-1-pentene-1-sulfonate C18H27NO5S 详情 详情
(IV) 51652 tert-butyl (1S,2E)-3-(chlorosulfonyl)-1-phenethyl-2-propenylcarbamate C16H22ClNO4S 详情 详情
(V) 51653 tert-butyl (1S,2E)-3-[[(benzyloxy)amino]sulfonyl]-1-phenethyl-2-propenylcarbamate C23H30N2O5S 详情 详情
(VI) 51654 (E,3S)-3-amino-N-(benzyloxy)-5-phenyl-1-pentene-1-sulfonamide C18H22N2O3S 详情 详情
(VII) 23627 (2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid C14H18N2O4 详情 详情
Extended Information