【结 构 式】 |
【分子编号】23171 【品名】bromo[4-(diethoxymethyl)phenyl]magnesium 【CA登记号】 |
【 分 子 式 】C11H15BrMgO2 【 分 子 量 】283.4479 【元素组成】C 46.61% H 5.33% Br 28.19% Mg 8.57% O 11.29% |
合成路线1
该中间体在本合成路线中的序号:(II)The reaction of 3-chloromethylpyridine (I) with the Grignard reagent of 4-bromobenzaldehyde diethylacetal (II) in THF gives 4-(3-pyridylmethyl)benzaldehyde diethylacetal (III), which is hydrolyzed with aqueous 1N HCl to 4-(3-pyridylmethyl)benzaldehyde (IV). The Wittig condensation of (IV) with 1-(ethoxycarbonyl)ethylidenetriphenylphosphorane (V) in CHCl3 affords 3-[4-(3-pyridylmethyl)phenyl]-2-methylacryl ic acid ethyl ester (VI), which is finally hydrolyzed with aqueous NaOH.
【1】 Tanouchi, T.; et al.; Pyridine derivatives. DE 2951786; FR 2445319; FR 2510108; GB 2039903; US 4271170; US 4317828 . |
【2】 Hillier, K.; Serradell, M.N.; Blancafort, P.; Castaner, J.; OKY-1581. Drugs Fut 1982, 7, 6, 399. |
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) | 15793 | 3-(Chloromethyl)pyridine | 3099-31-8 | C6H6ClN | 详情 | 详情 |
(II) | 23171 | bromo[4-(diethoxymethyl)phenyl]magnesium | C11H15BrMgO2 | 详情 | 详情 | |
(III) | 37069 | 3-[4-(diethoxymethyl)benzyl]pyridine; ethoxy[4-(3-pyridinylmethyl)phenyl]methyl ethyl ether | C17H21NO2 | 详情 | 详情 | |
(IV) | 37070 | 4-(3-pyridinylmethyl)benzaldehyde | C13H11NO | 详情 | 详情 | |
(V) | 37071 | ethyl 2-(triphenylphosphoranylidene)propanoate | 5717-37-3 | C23H23O2P | 详情 | 详情 |
(VI) | 37072 | ethyl (E)-2-methyl-3-[4-(3-pyridinylmethyl)phenyl]-2-propenoate | C18H19NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(V)Oxidation of disulfide (I) with sulfuryl chloride in AcOH at -20 C afforded (4-methoxyphenyl)sulfinyl chloride (II), which was condensed with (1R,2S)-2-phenylcyclohexanol to provide sulfinate (IV) as a single diastereomer. Subsequent condensation with the Grignard reagent (V) produced the chiral sulfoxide (VI). The diethyl acetal of (VI) was then hydrolyzed to the corresponding benzaldehyde (VII) using p-TsOH in THF-H2O. Finally, condensation of (VII) with N-cyclohexylpiperazine (VIII) using titanium tetraisopropoxide, followed by addition of diethylaluminum cyanide, furnished the target piperazinylacetonitrile.
【1】 Lowe, D.B.; Guzik, H.S.; Kozlowski, J.A.; et al.; Diphenyl sulfoxides as selective antagonists of the muscarinic M2 receptor. Bioorg Med Chem Lett 2000, 10, 20, 2255. |
【2】 Lowe, D.; Chang, W.; Kozlowski, J.; Berger, J.G.; McQuade, R.; Barnett, A.; Scherlock, M.; Tom, W.; Dugar, S.; Chen, L.-Y.; Clader, J.W.; Chackalamannil, S. (Schering Corp.); Benzylpiperidines and piperazines as muscarinic an. EP 0811002; JP 1999501014; US 5883096; WO 9626196 . |
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) | 23167 | 1-methoxy-4-[(4-methoxyphenyl)disulfanyl]benzene; bis(4-methoxyphenyl) disulfide | 5335-87-5 | C14H14O2S2 | 详情 | 详情 |
(II) | 23168 | 4-methoxybenzenesulfinyl chloride | C7H7ClO2S | 详情 | 详情 | |
(III) | 23169 | (1S,2R)-2-phenylcyclohexanol | C12H16O | 详情 | 详情 | |
(IV) | 23170 | (1S,2R)-2-phenylcyclohexyl 4-methoxybenzenesulfinate | C19H22O3S | 详情 | 详情 | |
(V) | 23171 | bromo[4-(diethoxymethyl)phenyl]magnesium | C11H15BrMgO2 | 详情 | 详情 | |
(VI) | 23172 | [4-(diethoxymethyl)phenyl](4-methoxyphenyl)oxo-lambda(4)-sulfane; 4-(diethoxymethyl)phenyl 4-methoxyphenyl sulfoxide | C18H22O4S | 详情 | 详情 | |
(VII) | 23173 | 4-[(4-methoxyphenyl)sulfinyl]benzaldehyde | C14H12O3S | 详情 | 详情 | |
(VIII) | 23174 | 1-cyclohexylpiperazine | 17766-28-8 | C10H20N2 | 详情 | 详情 |