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【结 构 式】 
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【分子编号】17829 【品名】2,2-dichloroacetyl chloride; dichloroacetyl chloride 【CA登记号】79-36-7 |
【 分 子 式 】C2HCl3O 【 分 子 量 】147.38744 【元素组成】C 16.3% H 0.68% Cl 72.16% O 10.86% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 2-amino-3'-chlorobenzophenone (I) with dichloroacetyl chloride (II) in acetone gives o-(m'-chlorobenzoyl)-2,2-dichloroacetanilide (III), which is cyclized with potassium cyanide in water yielding 2-amino-3-(m-chlorophenyl-3H-indol-3-ol (IV). Finally, this compound is condensed with 1,3-dibromopropane (A) in refluxing ethanol.
| 【1】 White, A.C.; Bell, S.C. (John Wyeth & Brother Ltd.); Process for the preparation of diazepino[1,2-a]indoles. CH 590286; DE 2417917; FR 2247227; GB 1427066; US 3931226 . |
| 【2】 Weetman, D.F.; Castaner, J.; Ciclazindol. Drugs Fut 1977, 2, 8, 508. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (I) | 40184 | (2-aminophenyl)(3-chlorophenyl)methanone | C13H10ClNO | 详情 | 详情 | |
| (II) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
| (III) | 40185 | 2,2-dichloro-N-[2-(3-chlorobenzoyl)phenyl]acetamide | C15H10Cl3NO2 | 详情 | 详情 | |
| (IV) | 40186 | 2-amino-3-(3-chlorophenyl)-3H-indol-3-ol | C14H11ClN2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：The partial acylation of 11beta,17a alpha(dihydroxy-D-homopregna-1,4-diene 3,20-dione (I) with 2,2-dichloroacetyl chloride gives the corresponding compound (II), which is acylated again with butyric anhydride yielding 17a alpha-butyryloxy-11beta-dichloroacetoxy-D-homopregna-1,4-diene-3,20-dione (III). Finally, this compound is hydrolyzed partially with aqueous NH4OH and methanol.
| 【1】 Furst, A.; Alig, L.; Kerb, U.; Muller, M.; Wiechert, R.; Kieslich, K. (Hoffmann-La Roche, Inc.); D-Homopregnanes. US 4202841 . |
| 【2】 Baines, A.; Muller, M.; Domoprednate. Drugs Fut 1987, 12, 2, 118. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 | |
| (I) | 22842 | (7R)-7-acetyl-5,7-dihydroxy-4a,6a-dimethyl-4b,5,6,6a,7,8,9,10,10a,10b,11,12-dodecahydro-2(4aH)-chrysenone | C22H30O4 | 详情 | 详情 | |
| (II) | 22843 | (7R)-7-acetyl-7-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,10,10a,10b,11,12-tetradecahydro-5-chrysenyl 2,2-dichloroacetate | C24H30Cl2O5 | 详情 | 详情 | |
| (III) | 22844 | (1R)-1-acetyl-11-[(2,2-dichloroacetyl)oxy]-10a,12a-dimethyl-8-oxo-1,2,3,4,4a,4b,5,6,8,10a,10b,11,12,12a-tetradecahydro-1-chrysenyl butyrate | C28H36Cl2O6 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)The reaction of 5-methoxyheptyl chloride (I) with magnesium in THF gives the corresponding Grignard reagent (II), which is condensed with 3-chlorocyclopentene (III) in refluxing THF to yield 3-(5-methoxy-1-heptyl)cyclopentene (IV). The cyclization of (IV) with dichloroacetyl chloride (V) by means of triethylamine in refluxing hexane affords 2-(5-methoxy-1-heptyl)-6,6-dichlorobicyclo[3.2.0]heptan-7-one (VI), which is submitted to a ring expansion with diazometane in ether giving 2-(5-methoxy-1-heptyl-6,6-dichlorobicyclo[3.3.0]octan-7-one (VII). Finally, this compound is dechlorinated with Zn in acetic acid.
| 【1】 Kasha, W.J. (CBD Corp.); Cycloaliphatic pharmaceutical cpds.. DE 3378265; EP 0107733; WO 8304019 . |
| 【2】 Castaner, R.M.; Castaner, J.; Serradell, M.N.; Cyoctol. Drugs Fut 1987, 12, 11, 1012. |
| 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) | 19539 | 1-chloro-5-methoxyheptane; 5-chloro-1-ethylpentyl methyl ether | C8H17ClO | 详情 | 详情 | |
| (II) | 19540 | chloro(5-methoxyheptyl)magnesium | C8H17ClMgO | 详情 | 详情 | |
| (III) | 19541 | 3-chloro-1-cyclopentene | C5H7Cl | 详情 | 详情 | |
| (IV) | 19542 | 5-(2-cyclopenten-1-yl)-1-ethylpentyl methyl ether; 3-(5-methoxyheptyl)-1-cyclopentene | C13H24O | 详情 | 详情 | |
| (V) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
| (VI) | 19544 | 7,7-dichloro-4-(5-methoxyheptyl)bicyclo[3.2.0]heptan-6-one | C15H24Cl2O2 | 详情 | 详情 | |
| (VII) | 19545 | 1,1-dichloro-4-(5-methoxyheptyl)hexahydro-2(1H)-pentalenone | C16H26Cl2O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VI)Hydrogenolysis of PNU-100542 (I) removed the benzyloxycarbonyl group and afforded secondary amine (II), which was acylated with (acetoxy)acetyl chloride (III) in the presence of triethylamine to provide amide PNU-142581 (IV). Then, acetate and phthaloyl protecting groups were both removed on treatment with an hydroalcoholic solution of methylamine, and the resulting aminoalcohol PNU-141718 (V) was N-acylated with dichloroacetyl chloride (VI) to yield the desired amide PNU-109230.
| 【1】 Ulanowicz, D.A.; et al.; Synthesis and biological activity of N-acetyl modified analogs of oxazolidinone anticancer agents linezolid and eperezolid. 37th Intersci Conf Antimicrob Agents Chemother (Sept 28-Oct 1, Toronto) 1997, Abst F-21. |
| 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) | 17824 | benzyl 4-(4-[(5S)-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1-piperazinecarboxylate | C30H27FN4O6 | 详情 | 详情 | |
| (II) | 17825 | 2-([(5S)-3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)-1H-isoindole-1,3(2H)-dione | C22H21FN4O4 | 详情 | 详情 | |
| (III) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (IV) | 17827 | 2-[4-(4-[(5S)-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1-piperazinyl]-2-oxoethyl acetate | C26H25FN4O7 | 详情 | 详情 | |
| (V) | 17828 | (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-glycoloyl-1-piperazinyl)phenyl]-1,3-oxazolidin-2-one | C16H21FN4O4 | 详情 | 详情 | |
| (VI) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Treatment of an excess of indole (I) with dichloroacetyl chloride (II) in the presence of AlCl3 under Friedel-Crafts conditions produced the trimer intermediate (III), which was cyclized and acylated to yield the title indolyl quinoline.
| 【1】 Chakrabarti, G.; et al.; Indolylquinoline derivatives are cytotoxic to Leishmania donovani promastigotes and amastigotes in vitro and are effective in treating murine visceral leishmaniasis. J Antimicrob Chemother 1999, 43, 3, 359. |
| 【2】 Mahato, S.B.; et al.; Synthesis of indolylquinolines under Friedel-Crafts reaction conditions. Tetrahedron 1994, 50, 36, 10803. |
合成路线6
该中间体在本合成路线中的序号：(III)The oxidative cleavage of prednisolone (I) using sodium metaperiodate produces carboxylic acid (II). Regioselective esterification of diol (II) with dichloroacetyl chloride (III) under phase-transfer conditions gives the 17-ester (IV). The title ethyl ester is then obtained by esterification of (IV) with iodoethane in the presence of NaHCO3 and tetrabutylammonium hydrogensulfate.
| 【1】 Bodor, N.S. (Soft Drugs, Inc.); Androstene derivs.. WO 9742214 . |
| 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) | 13538 | (8S,9S,10R,11S,13S,14S,17R)-17-Glycoloyl-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one; Prednisolone | 50-24-8 | C21H28O5 | 详情 | 详情 |
| (II) | 14612 | (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C20H26O5 | 详情 | 详情 | |
| (III) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
| (IV) | 58347 | (8S,9S,10R,11S,13S,14S,17R)-17-[(2,2-dichloroacetyl)oxy]-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C22H26Cl2O6 | 详情 | 详情 |