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【结 构 式】 
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【分子编号】18641 【品名】(1,3-dioxolan-2-ylmethyl)(triphenyl)phosphonium bromide 【CA登记号】52509-14-5 |
【 分 子 式 】C22H22BrO2P 【 分 子 量 】429.293242 【元素组成】C 61.55% H 5.17% Br 18.61% O 7.45% P 7.22% |
合成路线1
该中间体在本合成路线中的序号：(XI)Wittig reaction of 4-quinolinecarboxaldehyde (X) with dioxolanylmethyl phosphonium salt (XI) using potassium tert-butoxide in THF produced olefin (XII), which was reduced by catalytic hydrogenation to afford (XIII). Hydrolysis of acetal (XIII) with HCl in acetone-H2O gave quinolinylpropanal (XIV). Finally, reductive alkylation of N-aminoisoxazolone (VIII) with aldehyde (XIV) using NaBH3CN/AcOH in MeOH provided the target compound.
| 【1】 Agouridas, C.; Denis, A.; Auger, J.M.; Benedetti, Y.; Bonnefoy, A.; Bretin, F.; Chantot, J.F.; Dussarat, A.; Fromentin, C.; D'Ambrieres, S.G.; Lachaud, S.; Laurin, P.; Le Martret, O.; Loyau, V.; Tessot, N.; Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): A new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens. J Med Chem 1998, 41, 21, 4080. |
| 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) | 18638 | (3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-1-amino-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyloctahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazole-2,6,8,14(1H,7H,9H)-tetrone | C31H53N3O10 | 详情 | 详情 | |
| (X) | 18640 | 4-quinolinecarbaldehyde | 4363-93-3 | C10H7NO | 详情 | 详情 |
| (XI) | 18641 | (1,3-dioxolan-2-ylmethyl)(triphenyl)phosphonium bromide | 52509-14-5 | C22H22BrO2P | 详情 | 详情 |
| (XII) | 18642 | 4-[(E)-2-(1,3-dioxolan-2-yl)ethenyl]quinoline | C14H13NO2 | 详情 | 详情 | |
| (XIII) | 18643 | 4-[2-(1,3-dioxolan-2-yl)ethyl]quinoline | C14H15NO2 | 详情 | 详情 | |
| (XIV) | 18644 | 3-(4-quinolinyl)propanal | C12H11NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The intermediate aldehyde (VII) has been obtained as follows: The cyclization of 2-fluoro-4-hydrazinobenzonitrile (I) with malonaldehyde (II) by means of HCl in refluxing ethanol gives 2-fluoro-4-(1-pyrazolyl)benzonitrile (III), which is reduced by means of diisobutylaluminum hydride in toluene to yield the benzaldehyde (IV). The condensation of (IV) with (1,3-dioxolan-2-ylmethyl)triphenylphosphonium bromide (V) by means of TDA-1 and K2CO3 in refluxing dichloromethane to afford the 3-[2-fluoro-4-(1-pyrazolyl)phenyl]-2-propenal ethylene ketal (VI), which is finally hydrolyzed with HCl in THF to provide the target intermediate aldehyde (VII).
| 【1】 Henninger, T.C.; Xu, X.C. (Ortho-McNeil Pharmaceutical, Inc.); 6-O-Carbamoyl ketolide derivs. of erythromycin useful as antibacterials. US 6472372; WO 0246204 . |
| 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) | 58667 | 2-fluoro-4-hydrazinobenzonitrile | C7H6FN3 | 详情 | 详情 | |
| (II) | 58668 | 1,1,3,3-Tetramethoxypropane; Malonaldehyde bis(dimethylacetal); Malonaldehyde tetramethylacetal | 102-52-3 | C7H16O4 | 详情 | 详情 |
| (III) | 58669 | 2-fluoro-4-(1H-pyrazol-1-yl)benzonitrile | C10H6FN3 | 详情 | 详情 | |
| (IV) | 58670 | 2-fluoro-4-(1H-pyrazol-1-yl)benzaldehyde | C10H7FN2O | 详情 | 详情 | |
| (V) | 18641 | (1,3-dioxolan-2-ylmethyl)(triphenyl)phosphonium bromide | 52509-14-5 | C22H22BrO2P | 详情 | 详情 |
| (VI) | 58671 | 1-{4-[(E)-2-(1,3-dioxolan-2-yl)ethenyl]-3-fluorophenyl}-1H-pyrazole | C14H13FN2O2 | 详情 | 详情 | |
| (VII) | 58672 | (E)-3-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-2-propenal | C12H9FN2O | 详情 | 详情 |