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【结 构 式】 
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【分子编号】42364 【品名】1,3-diiodopropane 【CA登记号】627-31-6 |
【 分 子 式 】C3H6I2 【 分 子 量 】295.88958 【元素组成】C 12.18% H 2.04% I 85.78% |
合成路线1
该中间体在本合成路线中的序号：(XXV)The precursor cis-dodec-5-enoic acid (XXIX) was prepared as shown in Scheme 4. The lithium acetylide of 1-octyne (XXIV) was alkylated with 1,3-diiodopropane (XXV) to give the iodoalkyne (XXVI). Displacement of the iodide of (XXVI) with KCN in hot DMSO provided nitrile (XXVII), which was hydrolyzed to the corresponding carboxylic acid (XXVIII) employing KOH in ethylene glycol at 140 C. Partial hydrogenation of the triple bond in the presence of poisoned Lindlar catalyst furnished the (Z)-olefin (XXIX).
| 【1】 Christ, W.J.; Kawata, T.; Hawkins, L.D.; Kobayashi, S.; Asano, O.; Rossignol, D.P. (Eisai Co., Ltd.); Anti-endotoxin cpds.. EP 0536969; JP 1993194470; US 5530113 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 59091 | 1-octyne | C8H14 | 详情 | 详情 | |
| (XXV) | 42364 | 1,3-diiodopropane | 627-31-6 | C3H6I2 | 详情 | 详情 |
| (XXVI) | 59092 | 1-iodo-4-undecyne | C11H19I | 详情 | 详情 | |
| (XXVII) | 59093 | 5-dodecynenitrile | C12H19N | 详情 | 详情 | |
| (XXVIII) | 59094 | 5-dodecynoic acid | C12H20O2 | 详情 | 详情 | |
| (XXIX) | 49124 | (Z)-5-dodecenoic acid | C12H22O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Reaction of 1,3-diiodopropane (X) with two equivalents of vanillic acid (IX) in the presence of NaOH produced diacid (XI). Nitration of (XI) to give (XII) was carried out with concentrated HNO3 at -10 C. Dinitro diacid (XII) was then converted to the corresponding acid chloride (XIII) by treatment with oxalyl chloride. Coupling of acid chloride (XIII) with pyrrolidine (VIII) gave the bis-amide (XIV). After desilylation of (XIV) with tetrabutylammonium fluoride, the resultant bis-nitro-alcohol (XV) was reduced by means of SnCl2 to the diamine (XVI).
| 【2】 Thurston, D.E.; Howard, P.W. (University of Portsmouth); Compounds. EP 1109812; WO 0012508 . |
| 【1】 Kelland, L.R.; Gregson, S.J.; Brooks, N.A.; Jenkins, T.C.; Thurston, D.E.; Hartley, J.A.; Howard, P.W.; Adams, L.J.; Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity. J Med Chem 2001, 44, 5, 737. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 47735 | (2S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methylenepyrrolidine; tert-butyl(dimethyl)silyl [(2S)-4-methylenepyrrolidinyl]methyl ether | C12H25NOSi | 详情 | 详情 | |
| (IX) | 17786 | 4-hydroxy-3-methoxybenzoic acid; Vanillic acid | 121-34-6 | C8H8O4 | 详情 | 详情 |
| (X) | 42364 | 1,3-diiodopropane | 627-31-6 | C3H6I2 | 详情 | 详情 |
| (XI) | 47736 | 4-[3-(4-carboxy-2-methoxyphenoxy)propoxy]-3-methoxybenzoic acid | C19H20O8 | 详情 | 详情 | |
| (XII) | 47737 | 4-[3-(4-carboxy-2-methoxy-5-nitrophenoxy)propoxy]-5-methoxy-2-nitrobenzoic acid | C19H18N2O12 | 详情 | 详情 | |
| (XIII) | 47738 | 4-[3-[4-(chlorocarbonyl)-2-methoxy-5-nitrophenoxy]propoxy]-5-methoxy-2-nitrobenzoyl chloride | C19H16Cl2N2O10 | 详情 | 详情 | |
| (XIV) | 47739 | [(2S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methylenepyrrolidinyl][4-[3-(4-[[(2S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methylenepyrrolidinyl]carbonyl]-2-methoxy-5-nitrophenoxy)propoxy]-5-methoxy-2-nitrophenyl]methanone | C43H64N4O12Si2 | 详情 | 详情 | |
| (XV) | 47740 | [(2S)-2-(hydroxymethyl)-4-methylenepyrrolidinyl][4-[3-(4-[[(2S)-2-(hydroxymethyl)-4-methylenepyrrolidinyl]carbonyl]-2-methoxy-5-nitrophenoxy)propoxy]-5-methoxy-2-nitrophenyl]methanone | C31H36N4O12 | 详情 | 详情 | |
| (XVI) | 47741 | [2-amino-4-[3-(5-amino-4-[[(2S)-2-(hydroxymethyl)-4-methylenepyrrolidinyl]carbonyl]-2-methoxyphenoxy)propoxy]-5-methoxyphenyl][(2S)-2-(hydroxymethyl)-4-methylenepyrrolidinyl]methanone | C31H40N4O8 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Bishydroperoxide (III) was prepared by treatment of cyclododecanone (I) with hydrogen peroxide in formic acid or, alternatively, by ozonolysis of vinyl ether (II) in the presence of hydrogen peroxide at -70 C. Alkylation of bishydroperoxide (III) with 1,3-diiodopropane (IV) and CsOH in DMF furnished the title spirotetraoxane.
| 【1】 Tsuchiya, K.; et al.; Synthesis, crystal structure and anti-malarial activity of novel spiro-1,2,4,5-tetraoxacycloalkanes. Tetrahedron Lett 1999, 40, 21, 4077. |