(R)-benzyl 3-cyclohexyl-2-(((2S,3S,4R,5S,6R)-2-(ethylthio)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)oxy)propanoate -Drug Synthesis Database

【结构式】

【分子编号】68490

【品名】(R)-benzyl 3-cyclohexyl-2-(((2S,3S,4R,5S,6R)-2-(ethylthio)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)oxy)propanoate

【CA登记号】　

【分子式】C₂₄H₃₆O₇S

【分子量】468.612

【元素组成】C 61.51% H 7.74% O 23.90% S 6.84%

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)

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 .

参考文献中间体

合成目标

【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

Extended Information