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【结 构 式】

【分子编号】50048

【品名】methyl (2R,3R,4S)-3-amino-4-azido-2-[[phenethyl(propyl)amino]carbonyl]-3,4-dihydro-2H-pyran-6-carboxylate

【CA登记号】

【 分 子 式 】C19H25N5O4

【 分 子 量 】387.4388

【元素组成】C 58.9% H 6.5% N 18.08% O 16.52%

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:(VII)

Introduction of a Boc protecting group on derivative (I) by treatment with tert-butyldicarbonate and DMAP in dioxane affords 5-N-Boc derivative (II), which is then deacetylated by reaction with NaOMe in MeOH to provide compound (III). Conversion of trihydroxy derivative (III) into carboxylic acid (IV) is performed by first oxidation with sodium periodate in MeOH/H2O followed by treatment with sodium chlorite/potassium dihydrogen orthophosphate in tert-BuOH. Coupling of (IV) with secondary amine (V) by means of TBTU in THF yields phenethylpropyl carbamoyl derivative (VI), whose Boc group is removed by means of HCl in dioxane to give primary amine (VII). Condensation of (VII) with trifluoroacetic anhydride (VIII) in pyridine furnishes trifluoroacetylamino derivative (IX), whose azide group is reduced by means of PPh3 and Et3N in THF/H2O to yield 4-amino derivative (X). Finally, the desired product is obtained by saponification of the methyl ester group of (X) by heating with Et3N in H2O.

1 Smith, P.W.; et al.; Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino-Neu5Ac2en (GG167) with modified 5-substituents. Eur J Med Chem 1996, 31, 2, 143.
2 Fulton, H.E.; Jack, T.I.; Coomber, B.A.; Colman, P.; Wonacott, A.J.; Varghese, J.; Evans, D.N.; Wyatt, P.G.; Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides. Bioorg Med Chem Lett 2001, 11, 5, 669.
3 Smith, P.; Sollis, S.; Cherry, P.; Howes, P. (Biota Scientific Management Pty Ltd.); 6-Carboxamido dihydropyran derivs.. US 5990156; WO 9636628 .
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) 15979 methyl (2R,3R,4S)-3-(acetamido)-4-azido-2-[(1S,2R)-1,2,3-tris(acetoxy)propyl]-3,4-dihydro-2H-pyran-6-carboxylate C18H24N4O10 详情 详情
(II) 50043 methyl (2R,3R,4S)-3-[acetyl(tert-butoxycarbonyl)amino]-4-azido-2-[(1S,2R)-1,2,3-tris(acetoxy)propyl]-3,4-dihydro-2H-pyran-6-carboxylate C23H32N4O12 详情 详情
(III) 50044 methyl (2R,3R,4S)-4-azido-3-[(tert-butoxycarbonyl)amino]-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate C15H24N4O8 详情 详情
(IV) 50045 (2R,3R,4S)-4-azido-3-[(tert-butoxycarbonyl)amino]-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-2-carboxylic acid C13H18N4O7 详情 详情
(V) 50046 N-phenethyl-1-propanamine; N-phenethyl-N-propylamine C11H17N 详情 详情
(VI) 50047 methyl (2R,3R,4S)-4-azido-3-[(tert-butoxycarbonyl)amino]-2-[[phenethyl(propyl)amino]carbonyl]-3,4-dihydro-2H-pyran-6-carboxylate C24H33N5O6 详情 详情
(VII) 50048 methyl (2R,3R,4S)-3-amino-4-azido-2-[[phenethyl(propyl)amino]carbonyl]-3,4-dihydro-2H-pyran-6-carboxylate C19H25N5O4 详情 详情
(VIII) 33862 trifluoroacetic anhydride 407-25-0 C4F6O3 详情 详情
(IX) 50049 methyl (2R,3R,4S)-4-azido-2-[[phenethyl(propyl)amino]carbonyl]-3-[(2,2,2-trifluoroacetyl)amino]-3,4-dihydro-2H-pyran-6-carboxylate C21H24F3N5O5 详情 详情
(X) 50050 methyl (2R,3R,4S)-4-amino-2-[[phenethyl(propyl)amino]carbonyl]-3-[(2,2,2-trifluoroacetyl)amino]-3,4-dihydro-2H-pyran-6-carboxylate C21H26F3N3O5 详情 详情
Extended Information