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【结 构 式】 
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【分子编号】27507 【品名】2,6-dichlorobenzaldehyde 【CA登记号】83-38-5 |
【 分 子 式 】C7H4Cl2O 【 分 子 量 】175.01356 【元素组成】C 48.04% H 2.3% Cl 40.51% O 9.14% |
合成路线1
该中间体在本合成路线中的序号：(I)By condensation of 2,6-dichlorobenzaldehyde (I) and aminoguanidine carbonate (II).
| 【1】 Bundgaard, H.; Castaner, J.; Guanabenz. Drugs Fut 1976, 1, 11, 523. |
| 【2】 Wuesthoff, F.; et al.; Novel hydrazine compounds and compositions containing them. BE 0661193; CH 453793; DE 1567104; FR 1455835; GB 1019120 . |
合成路线2
该中间体在本合成路线中的序号：(I)Nitration of 2,6-dichlorobenzaldehyde (I) with 70% HNO3 in concentrated H2SO4 at ice-bath temperature provided the 3-nitro derivative (II). This was reduced with NaBH4 in MeOH at 10 C to the alcohol (III), which was treated with mesyl chloride and triethylamine in dichloromethane to give mesylate (IV). Alkylation of 5-hydroxyisoquinoline (V) with mesylate (IV) in the presence of NaH in DMF yielded ether (VI). Subsequent reduction of the nitro group of (VI) with hydrazine and FeCl3 provided amine (VII), which was finally acylated with Ac2O in dichloroethane at 70 C to furnish the target acetamide.
| 【1】 Satoh, S.; Kayakiri, H.; Abe, Y.; et al.; A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 1. Construction of the basic framework. J Med Chem 1998, 41, 4, 564. |
| 【2】 Yoshida, Y.; Barrett, D.; Azami, H.; Morinaga, C.; Matsumoto, Y.; Takasugi, H.; Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity. Bioorg Med Chem Lett 1998, 8, 14, 1897. |
| 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) | 27507 | 2,6-dichlorobenzaldehyde | 83-38-5 | C7H4Cl2O | 详情 | 详情 |
| (II) | 27508 | 2,6-dichloro-3-nitrobenzaldehyde | C7H3Cl2NO3 | 详情 | 详情 | |
| (III) | 18590 | (2,6-dichloro-3-nitrophenyl)methanol | C7H5Cl2NO3 | 详情 | 详情 | |
| (IV) | 19295 | 2,6-dichloro-3-nitrobenzyl methanesulfonate | C8H7Cl2NO5S | 详情 | 详情 | |
| (V) | 18668 | 5-isoquinolinol | 2439-04-5 | C9H7NO | 详情 | 详情 |
| (VI) | 27509 | 2,6-dichloro-3-nitrobenzyl 5-isoquinolinyl ether | C16H10Cl2N2O3 | 详情 | 详情 | |
| (VII) | 27510 | 2,4-dichloro-3-[(5-isoquinolinyloxy)methyl]aniline | C16H12Cl2N2O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Cyclization of the diaminoacrylate (I) with bis(2,4,6-trichlorophenyl) malonate (II) in hot toluene produced pyridone (III). This was then condensed with 2,6-dichlorobenzaldehyde (IV) in the presence of piperidine in refluxing EtOH to furnish the title bis-pyridyl derivative.
| 【1】 Onnis, V.; Cocco, M.T.; Congiu, C.; Synthesis and antitumor activity of 4-hydroxy-2-pyridone derivatives. Eur J Med Chem 2000, 35, 5, 545. |
| 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) | 47074 | ethyl (Z)-3-amino-3-(4-morpholinyl)-2-propenoate | C9H16N2O3 | 详情 | 详情 | |
| (II) | 12956 | bis(2,4,6-trichlorophenyl) malonate | C15H6Cl6O4 | 详情 | 详情 | |
| (III) | 47075 | ethyl 4-hydroxy-2-(4-morpholinyl)-6-oxo-1,6-dihydro-3-pyridinecarboxylate | C12H16N2O5 | 详情 | 详情 | |
| (IV) | 27507 | 2,6-dichlorobenzaldehyde | 83-38-5 | C7H4Cl2O | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)2,6-Dichlorobenzaldehyde (I) was converted to oxime (II) and then chlorinated with N-chlorosuccinimide to afford the oximidoyl chloride (III). The cycloaddition reaction between ketoester (IV) and the nitrile oxide resulting from (III) in the presence of NaOMe gave rise to the isoxazole system (V). The ester group of (V) was then reduced to alcohol (VI) employing diisobutylaluminium hydride. Subsequent coupling of alcohol (VI) with 2-chloro-4-hydroxybenzaldehyde (VII) under Mitsunobu conditions provided ether (VIII). Phosphonate (X) was prepared by heating methyl 3-(bromomethyl)benzoate (IX) with triethyl phosphite at 185 C. Horner-Emmons condensation of aldehyde (VIII) with phosphonate (X) in the presence of NaH in THF furnished the stilbene derivative (XI). The methyl ester group of (XI) was finally hydrolyzed by means of LiOH in aqueous THF.
| 【1】 Lehmann, J.; Stimmel, J.B.; Blanchard, S.G.; Kliewer, S.A.; Willson, T.M.; Parks, D.J. (Glaxo Group Ltd.); Assays for ligands for nuclear receptors. WO 0037077 . |
| 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) | 27507 | 2,6-dichlorobenzaldehyde | 83-38-5 | C7H4Cl2O | 详情 | 详情 |
| (II) | 43329 | 2,6-dichlorobenzaldehyde oxime | C7H5Cl2NO | 详情 | 详情 | |
| (III) | 43330 | 2,6-dichloro-N-hydroxybenzenecarboximidoyl chloride | C7H4Cl3NO | 详情 | 详情 | |
| (IV) | 43331 | methyl 4-methyl-3-oxopentanoate | 42558-54-3 | C7H12O3 | 详情 | 详情 |
| (V) | 43332 | methyl 3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolecarboxylate | C14H13Cl2NO3 | 详情 | 详情 | |
| (VI) | 43333 | [3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methanol | C13H13Cl2NO2 | 详情 | 详情 | |
| (VII) | 43334 | 2-chloro-4-hydroxybenzaldehyde | C7H5ClO2 | 详情 | 详情 | |
| (VIII) | 43335 | 2-chloro-4-[[3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methoxy]benzaldehyde | C20H16Cl3NO3 | 详情 | 详情 | |
| (IX) | 20392 | methyl 3-(bromomethyl)benzoate | 1129-28-8 | C9H9BrO2 | 详情 | 详情 |
| (X) | 43336 | methyl 3-[(diethoxyphosphoryl)methyl]benzoate | C13H19O5P | 详情 | 详情 | |
| (XI) | 43337 | methyl 3-[(E)-2-(2-chloro-4-[[3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methoxy]phenyl)ethenyl]benzoate | C29H24Cl3NO4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)The title diaryl thiazolidinone was synthesized by condensation between 2,6-dichlorobenzaldehyde (I), 2-amino-6-methylpyridine (II) and mercaptoacetic acid (III) in refluxing toluene.
| 【1】 Barreca, M.L.; et al.; Discovery of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV-1 agents. Bioorg Med Chem Lett 2001, 11, 13, 1793. |