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【结 构 式】 
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【分子编号】68491 【品名】orotic acid chloride;Orotoylchloride;Orotyl chloride;1,2,3,6-tetrahydro-2,6-dioxo-4-Pyrimidinecarbonylchloride 【CA登记号】3346-64-3 |
【 分 子 式 】C5H3ClN2O3 【 分 子 量 】174.5432 【元素组成】C 34.41% H 1.73% Cl 20.31% N 16.05% O 27.5% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Intermediate (V) is prepared by treatment of ethyl β-D-thiogalactopyranoside (VII) with Bu2SnO in MeOH, followed by regioselective alkylation with triflate (VIII) in the presence of CsF in DME to afford ether (IX), which by subsequent esterification with benzoyl chloride (X) by means of pyridine and DMAP gives tribenzoate (XI). Coupling of thioglycoside (XI) with the acceptor alcohol (XII) in the presence of DMTST in CH2Cl2 yields adduct (XIII), which is then subjected to reductive acylation with orotic acid chloride (XIV) by means of PPh3 in CH2Cl2 to provide amide (XV). Finally, compound (XV) is debenzylated by hydrogenolysis with H2 over Pd/C in dioxane/H2O, followed by selective didebenzoylation by means of NaOMe in MeOH .
| 【1】 Magnani, J.L., Patton, J.T. Jr., Sarkar, A.K., Svarovsky, S.A., Ernst, B. (GlycoMimetics, Inc.). Heterobifunctional pan-selectin inhibitors. EP 1934236, EP 2264043, JP 2009507031, US 2007054870, US 7728117, WO 2007028050. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 68486 | (2R)-2-(((2S,3S,4R,5R,6S)-2-(((1S,3R,5S)-5-((2-aminoethyl)carbamoyl)-3-(2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-2-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexyl)oxy)-3-(benzoyloxy)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)oxy)-3-cyclohexylpropanoic acid | C41H55N3O19 | 详情 | 详情 | |
| (VII) | 68488 | Ethyl 1-thio-β-D-galactopyranoside;Ethyl 1-deoxy-1-thio-β-D-galactopyranoside;(2S,3S,4R,5S,6R)-2-(ethylthio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;β-D-thiogalactopyranoside | 56245-60-4 | C8H16O5S | 详情 | 详情 |
| (VIII) | 68489 | (R)-benzyl 3-cyclohexyl-2-(((trifluoromethyl)sulfonyl)oxy)propanoate | C17H21F3O5S | 详情 | 详情 | |
| (IX) | 68490 | (R)-benzyl 3-cyclohexyl-2-(((2S,3S,4R,5S,6R)-2-(ethylthio)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)oxy)propanoate | C24H36O7S | 详情 | 详情 | |
| (X) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (XI) | 68495 | (2S,3S,4R,5S,6R)-2-((benzoyloxy)methyl)-4-(((R)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl)oxy)-6-(ethylthio)tetrahydro-2H-pyran-3,5-diyl dibenzoate | C45H48O10S | 详情 | 详情 | |
| (XII) | 68493 | (1S,3S,4R,5R)-methyl 3-azido-5-hydroxy-4-(((2S,3S,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexanecarboxylate | C35H41N3O8 | 详情 | 详情 | |
| (XIII) | 68494 | (2S,3S,4R,5S,6R)-2-(((2S,5S)-3-azido-5-(methoxycarbonyl)-2-(((2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexyl)oxy)-6-((benzoyloxy)methyl)-4-(((R)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl)oxy)tetrahydro-2H-pyran-3,5-diyl dibenzoate | C78H83N3O18 | 详情 | 详情 | |
| (XIV) | 68491 | orotic acid chloride;Orotoylchloride;Orotyl chloride;1,2,3,6-tetrahydro-2,6-dioxo-4-Pyrimidinecarbonylchloride | 3346-64-3 | C5H3ClN2O3 | 详情 | 详情 |
| (XV) | 68492 | (2S,3S,4R,5S,6R)-2-((benzoyloxy)methyl)-4-(((R)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl)oxy)-6-(((2S,3R,5S)-3-(2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-5-(methoxycarbonyl)-2-(((2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexyl)oxy)tetrahydro-2H-pyran-3,5-diyl dibenzoate | C83H87N3O21 | 详情 | 详情 |