【结 构 式】 |
【分子编号】52038 【品名】ethyl 1-[2-([2,3-dichloro-4-[(1R,2S)-2-([[3-(2-oxo-1-pyrrolidinyl)propyl]amino]carbonyl)cyclopropyl]phenyl]sulfanyl)phenyl]-3-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C31H37Cl2N3O4S 【 分 子 量 】618.624 【元素组成】C 60.19% H 6.03% Cl 11.46% N 6.79% O 10.35% S 5.18% |
合成路线1
该中间体在本合成路线中的序号:(XII)2,3-Dichloro-4-hydroxybenzaldehyde (I) was converted to the corresponding aryl triflate (II), which was subsequently condensed with 2-bromothiophenol (III), yielding the diaryl sulfide (IV). Wittig reaction of aldehyde (IV) with the ylide resulting from the phosphonium salt (V) afforded the unsaturated ester (VI). Cycloaddition between (VI) and the in situ-generated dimethylsulfoxonium methylide gave rise to the cyclopropane derivative (VII). After basic hydrolysis of the ethyl ester (VII), the resultant carboxylic acid (VIII) was coupled with 1-(3-aminopropyl)-2-pyrrolidinone (IX), providing amide (X). Displacement of the aryl bromide group of (X) with ethyl nipecotate (XI) in the presence of BINAP and Pd catalysts furnished the piperidine-substituted compound (XII). The ethyl ester group of (XII) was finally hydrolyzed to the target carboxylic acid under basic conditions.
【1】 Link, J.T.; et al.; Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction antagonists. Bioorg Med Chem Lett 2001, 11, 8, 973. |
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) | 52028 | 2,3-dichloro-4-hydroxybenzaldehyde | C7H4Cl2O2 | 详情 | 详情 | |
(II) | 52029 | 2,3-dichloro-4-formylphenyl trifluoromethanesulfonate | C8H3Cl2F3O4S | 详情 | 详情 | |
(III) | 52030 | 2-Bromobenzenethiol; 2-Bromothiophenol;2-bromo-benzenethio;2-Bromo thiophenol | 6320-02-1 | C6H5BrS | 详情 | 详情 |
(IV) | 52031 | 4-[(2-bromophenyl)sulfanyl]-2,3-dichlorobenzaldehyde | C13H7BrCl2OS | 详情 | 详情 | |
(V) | 52032 | (2-ethoxy-2-oxoethyl)(triphenyl)phosphonium chloride | C22H22ClO2P | 详情 | 详情 | |
(VI) | 52033 | ethyl (E)-3-[4-[(2-bromophenyl)sulfanyl]-2,3-dichlorophenyl]-2-propenoate | C17H13BrCl2O2S | 详情 | 详情 | |
(VII) | 52034 | ethyl (1S,2R)-2-[4-[(2-bromophenyl)sulfanyl]-2,3-dichlorophenyl]cyclopropanecarboxylate | C18H15BrCl2O2S | 详情 | 详情 | |
(VIII) | 52035 | (1S,2R)-2-[4-[(2-bromophenyl)sulfanyl]-2,3-dichlorophenyl]cyclopropanecarboxylic acid | C16H11BrCl2O2S | 详情 | 详情 | |
(IX) | 52036 | N-(3-Aminopropyl)-2-pyrrolidinone; N-(3'-Aminopropyl)-2-pyrrolidinone | 7663-77-6 | C7H14N2O | 详情 | 详情 |
(X) | 52037 | (1S,2R)-2-[4-[(2-bromophenyl)sulfanyl]-2,3-dichlorophenyl]-N-[3-(2-oxo-1-pyrrolidinyl)propyl]cyclopropanecarboxamide | C23H23BrCl2N2O2S | 详情 | 详情 | |
(XI) | 25693 | ethyl 3-piperidinecarboxylate | 5006-62-2 | C8H15NO2 | 详情 | 详情 |
(XII) | 52038 | ethyl 1-[2-([2,3-dichloro-4-[(1R,2S)-2-([[3-(2-oxo-1-pyrrolidinyl)propyl]amino]carbonyl)cyclopropyl]phenyl]sulfanyl)phenyl]-3-piperidinecarboxylate | C31H37Cl2N3O4S | 详情 | 详情 |