【结 构 式】 |
【分子编号】67638 【品名】methyl 1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropanecarboxylate 【CA登记号】 |
【 分 子 式 】C15H18O5 【 分 子 量 】278.30492 【元素组成】C 64.74% H 6.52% O 28.74% |
合成路线1
该中间体在本合成路线中的序号:(XV)Condensation of 4-hydroxy-3-methoxyacetophenone (XIII) with mesylate (XIV) by means of K2CO3 in DMF at 100 °C yields the aryl ether (XV), which by nitration using HNO3 in AcOH gives the corresponding o-nitroaryl ketone (XVI). Reduction of the nitro group in compound (XVI) using Fe and NH4Cl in refluxing EtOH/H2O gives amine (XVII). Friedlaender cyclization of the o-aminoaryl ketone (XVII) with ethyl formate (XVIII) and NaOMe in DME affords a 4-hydroxyquinoline derivative, which without isolation is chlorinated using POCl3 to produce the corresponding chloride (XIX). Condensation of the aryl chloride (XIX) with 6-hydroxy-N-methyl-1-naphthamide (V) in the presence of DMAP in refluxing dioxane gives adduct (XX), whose methyl ester is hydrolyzed with NaOH in refluxing MeOH to afford acid (XXI). Activation of acid (XXI) with i-BuOCOCl in the presence of DIEA in acetone and subsequent substitution of the obtained mixed anhydride with NaN3 produces azide (XXII), which is finally treated with PhCH2OH in refluxing toluene .
【1】 Chen, G.P. (Advenchen Laboratories, LLC). Spiro substituted compounds as angiogenesis inhibitors. KR 2015039889; US 8163923; EP 2125777; JP 2010521474; WO 2008112408; US 2008227812. |
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) | 67629 | 6-hydroxy-N-methyl-1-naphthamide | C12H11NO2 | 详情 | 详情 | |
(XIII) | 22604 | 1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone | 498-02-2 | C9H10O3 | 详情 | 详情 |
(XIV) | 67637 | 1-(4-hydroxy-3-methoxyphenyl)ethanone | C7H12O5S | 详情 | 详情 | |
(XV) | 67638 | methyl 1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropanecarboxylate | C15H18O5 | 详情 | 详情 | |
(XVI) | 67639 | methyl 1-((4-acetyl-2-methoxy-5-nitrophenoxy)methyl)cyclopropanecarboxylate | C15H17NO7 | 详情 | 详情 | |
(XVII) | 67640 | methyl 1-((4-acetyl-5-amino-2-methoxyphenoxy)methyl)cyclopropanecarboxylate | C15H19NO5 | 详情 | 详情 | |
(XVIII) | 16602 | ethyl formate | 109-94-4 | C3H6O2 | 详情 | 详情 |
(XIX) | 67641 | methyl 1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropanecarboxylate | C16H16ClNO4 | 详情 | 详情 | |
(XX) | 67642 | methyl 1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarboxylate | C28H26N2O6 | 详情 | 详情 | |
(XXI) | 67643 | 1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarboxylic acid | C27H24N2O6 | 详情 | 详情 | |
(XXII) | 67644 | 1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarbonyl azide | C27H23N5O5 | 详情 | 详情 |