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【结 构 式】

【分子编号】22841

【品名】benzyl (1S)-1-([3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]-4-hydroxy-1-pyrrolidinyl]carbonyl)-3-methylbutylcarbamate

【CA登记号】

【 分 子 式 】C32H44N4O7

【 分 子 量 】596.72412

【元素组成】C 64.41% H 7.43% N 9.39% O 18.77%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

3-Pyrroline (I) was protected with di-tert-buyl dicarbonate to give N-Boc-pyrroline (II), which was then epoxidized with meta-chloroperbenzoic acid. The resulting epoxide (III) was opened with sodium azide in aqueous MeOH to yield trans-azidoalcohol (IV). Subsequent reduction of the azide (IV) to aminoalcohol (V) was effected by hydrogenation over Pd/C (1). Condensation of the racemic trans-aminoalcohol (V) with N-Cbz-L-leucine (VI) in the presence of EDC and HOBt provided amide (VII) as a diastereomeric mixture. The N-Boc group of (VII) was then deprotected with HCl in EtOAc, and the resulting amine (VIII) was coupled with another N-Cbz-L-leucine (VI) unit to give (IX). Oxidation of the alcohol group of (IX) to the target ketone was accomplished with Jones reagent in acetone. The diastereomeric mixture was separated by reverse phase-HPLC, however the diastereomers were not configurationally stable and reequilibrated spontaneusly to the original mixture.

1 Marquis, R.W.; Yamashita, D.S.; Ru, Y.; LoCastro, S.M.; Oh, H.J.; Erhard, K.F.; DesJarlais, R.L.; Head, M.S.; Smith, W.W.; Zhao, B.; Janson, C.A.; Abdel-Meguid, S.S.; Tomaszek, T.A.; Levy, M.A.; Veber, D.F.; Conformationally constrained 1,3-diamino ketones: a series of potent inhibitors of the cysteine protease cathepsin K. J Med Chem 1998, 41, 19, 3563.
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) 22833 2,5-dihydro-1H-pyrrole;3-Pyrroline 109-96-6 C4H7N 详情 详情
(II) 22834 2,5-Dihydro-1H-pyrrole-1-carboxylic acid 1,1-d;2,5-Dihydropyrrole-1-carboxylic acid tert-butyl ester;tert-Butyl 2H-pyrrole-1(5H)-carboxylate;1-tert-Butoxycarbonylpyrroline;tert-butyl 2,5-dihydro-1H-pyrrole-1-carboxylate 73286-70-1 C9H15NO2 详情 详情
(III) 22835 tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate C9H15NO3 详情 详情
(IV) 22836 tert-butyl (3R,4S)-3-azido-4-hydroxy-1-pyrrolidinecarboxylate 143700-05-4 C9H16N4O3 详情 详情
(V) 22837 tert-butyl (3S,4S)-3-amino-4-hydroxy-1-pyrrolidinecarboxylate 190792-74-6 C9H18N2O3 详情 详情
(VI) 22838 (2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoic acid C14H19NO4 详情 详情
(VII) 22839 tert-butyl 3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]-4-hydroxy-1-pyrrolidinecarboxylate C23H35N3O6 详情 详情
(VIII) 22840 benzyl (1S)-1-[[(4-hydroxy-3-pyrrolidinyl)amino]carbonyl]-3-methylbutylcarbamate C18H27N3O4 详情 详情
(IX) 22841 benzyl (1S)-1-([3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]-4-hydroxy-1-pyrrolidinyl]carbonyl)-3-methylbutylcarbamate C32H44N4O7 详情 详情
Extended Information