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【结 构 式】 
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【药物名称】Acrivastine, BW-825C, Semprex 【化学名称】(E,E)-3-[6-[1-(4-Methylphenyl)-3-(1-pyrroldidinyl)-1-propenyl]-2-pyridinyl]-2-propenoic acid 【CA登记号】87848-99-5 【 分 子 式 】C22H24N2O2 【 分 子 量 】348.44878 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Allergic Skin Disorders, Treatment for, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Urticaria, Treatment for, Histamine H1 Antagonists |
合成路线1
A synthesis of deuterium-labeled acrivastine has been published. The reaction of 2,6-dibromopyridine (I) with butyllithium in ethyl ether gives the monolithium salt (II), which is condensed with perdeuterated 4-methylbenzaldehyde (III) in the same solvent to yield the methanol (IV). The oxidation of (IV) with pyridinium chlorochromate in dichloromethane affords the corresponding ketone (V), which is condensed with ethyl acrylate (VI) by means of palladium acetate, triphenylphosphine and tributylamine at 130 C to give 3-[6-([2H]-4-methylbenzoyl)pyridin-2-yl]acrylic acid ethyl ester (VII). The Wittig condensation of (VII) with triphenyl[2-(1-pyrrolidinyl)ethyl]phosphonium bromide (VIII) by means of butyllithium in THF affords a cis:trans mixture that is submitted to chromatography yielding the (E,E)-isomer (IX), which is finally hydrolyzed with NaOH in ethanol, at room temperature.
| 【1】 Thompson, J.B.; Blake, K.W.; McNutt, R.W.; Synthesis of deuterium-labeled acrivastine and an acrivastine metabolite. J Label Compd Radiopharm 1995, 36, 10, 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) | 10159 | 2,6-Dibromopyridine | 626-05-1 | C5H3Br2N | 详情 | 详情 |
| (II) | 10160 | (6-Bromo-2-pyridinyl)lithium | C5H3BrLiN | 详情 | 详情 | |
| (III) | 10161 | 4-Methylbenzaldehyde | 104-87-0 | C8H8O | 详情 | 详情 |
| (III) | 44590 | 4-methylbenzaldehyde | C8H8O | 详情 | 详情 | |
| (IV) | 10162 | (6-Bromo-2-pyridinyl)(4-methylphenyl)methanol | C13H12BrNO | 详情 | 详情 | |
| (IV) | 44591 | (6-bromo-2-pyridinyl)(4-methylphenyl)methanol | C13H12BrNO | 详情 | 详情 | |
| (V) | 10163 | (6-Bromo-2-pyridinyl)(4-methylphenyl)methanone | C13H10BrNO | 详情 | 详情 | |
| (V) | 44592 | (6-bromo-2-pyridinyl)(4-methylphenyl)methanone | C13H10BrNO | 详情 | 详情 | |
| (VI) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (VII) | 10165 | ethyl (E)-3-[6-(4-methylbenzoyl)-2-pyridinyl]-2-propenoate | C18H17NO3 | 详情 | 详情 | |
| (VII) | 44593 | ethyl (E)-3-[6-(4-methylbenzoyl)-2-pyridinyl]-2-propenoate | C18H17NO3 | 详情 | 详情 | |
| (VIII) | 10166 | Triphenyl[2-(1-pyrrolidinyl)ethyl]phosphonium bromide | C24H27BrNP | 详情 | 详情 | |
| (IX) | 10167 | ethyl (E)-3-[6-[(E)-1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]-2-pyridinyl]-2-propenoate | C24H28N2O2 | 详情 | 详情 | |
| (IX) | 44594 | ethyl (E)-3-[6-[(E)-1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]-2-pyridinyl]-2-propenoate | C24H28N2O2 | 详情 | 详情 |