【结 构 式】 |
【分子编号】51303 【品名】ethyl (E)-3-(3-nitrophenyl)-3-(3-pyridinyl)-2-propenoate 【CA登记号】 |
【 分 子 式 】C16H14N2O4 【 分 子 量 】298.29824 【元素组成】C 64.42% H 4.73% N 9.39% O 21.45% |
合成路线1
该中间体在本合成路线中的序号:(IIIa)Nitration of 3-benzoylpyridine (I) with KNO3 in sulfuric acid yielded the meta-nitrobenzoyl derivative (II). Wadsworth-Emmons reaction of ketone (II) with triethyl phosphonoacetate produced the unsaturated ester (IIIa-b) as a mixture of geometric isomers. Nitro group reduction in (IIIa-b) employing Fe and HCl gave aniline (IVa-b), which was condensed with 4-methoxybenzenesulfonyl chloride (V) to afford sulfonamide (VIa-b). After conversion of the pyridine ring of (VIa-b) to the corresponding N-oxide (VIIa-b) with m-chloroperbenzoic acid, the sulfonamide N atom of (VIIa-b) was alkylated with isopropyl iodide and K2CO3 to produce (VIIIa-b). Reduction of the N-oxide of (VIIIa-b) by means of Fe and HOAc, followed by basic hydrolysis of the ethyl ester, furnished acid (IXa-b). This was then coupled with O-t-butyldimethylsilyl hydroxylamine to provide, after separation of the Z/E isomeric mixture, the desired hydroxamic acid.
【1】 Hirata, T.; et al.; Discovery of potent, highly selective, and orally active propenohydroxamate TNF-alpha converting enzyme (TACE) inhibitors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 262. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IIIa) | 51303 | ethyl (E)-3-(3-nitrophenyl)-3-(3-pyridinyl)-2-propenoate | C16H14N2O4 | 详情 | 详情 | |
(IIIb) | 51304 | ethyl (Z)-3-(3-nitrophenyl)-3-(3-pyridinyl)-2-propenoate | C16H14N2O4 | 详情 | 详情 | |
(IVa) | 51305 | ethyl (E)-3-(3-aminophenyl)-3-(3-pyridinyl)-2-propenoate | C16H16N2O2 | 详情 | 详情 | |
(IVb) | 51306 | ethyl (Z)-3-(3-aminophenyl)-3-(3-pyridinyl)-2-propenoate | C16H16N2O2 | 详情 | 详情 | |
(VIa) | 51307 | ethyl (E)-3-(3-[[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-(3-pyridinyl)-2-propenoate | C23H22N2O5S | 详情 | 详情 | |
(VIb) | 51308 | ethyl (Z)-3-(3-[[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-(3-pyridinyl)-2-propenoate | C23H22N2O5S | 详情 | 详情 | |
(VIIa) | 51309 | 3-[(E)-3-ethoxy-1-(3-[[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-oxo-1-propenyl]-1-pyridiniumolate | C23H22N2O6S | 详情 | 详情 | |
(VIIb) | 51310 | 3-[(Z)-3-ethoxy-1-(3-[[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-oxo-1-propenyl]-1-pyridiniumolate | C23H22N2O6S | 详情 | 详情 | |
(VIIIa) | 51311 | 3-[(Z)-3-ethoxy-1-(3-[isopropyl[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-oxo-1-propenyl]-1-pyridiniumolate | C26H28N2O6S | 详情 | 详情 | |
(VIIIb) | 51312 | 3-[(E)-3-ethoxy-1-(3-[isopropyl[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-oxo-1-propenyl]-1-pyridiniumolate | C26H28N2O6S | 详情 | 详情 | |
(IXa) | 51313 | (E)-3-(3-[isopropyl[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-(3-pyridinyl)-2-propenoic acid | C24H24N2O5S | 详情 | 详情 | |
(IXb) | 51314 | (Z)-3-(3-[isopropyl[(4-methoxyphenyl)sulfonyl]amino]phenyl)-3-(3-pyridinyl)-2-propenoic acid | C24H24N2O5S | 详情 | 详情 | |
(I) | 27766 | phenyl(3-pyridinyl)methanone | 5424-19-1 | C12H9NO | 详情 | 详情 |
(II) | 51302 | (3-nitrophenyl)(3-pyridinyl)methanone | C12H8N2O3 | 详情 | 详情 | |
(V) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |