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【结 构 式】 
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【分子编号】39908 【品名】1-(3,3,3-trifluoro-2-oxopropyl)pyridinium bromide 【CA登记号】 |
【 分 子 式 】C8H7BrF3NO 【 分 子 量 】270.0489296 【元素组成】C 35.58% H 2.61% Br 29.59% F 21.11% N 5.19% O 5.92% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of trifluoroacetylmethylpyridinium bromide (I) with 3-(4-trifluoromethylbenzoyl)acrylic acid (II) by means of ammonium acetate in refluxing methanol gives 2-trifluoromethyl-6-(4-trifluoromethylphenyl)isonicotinic acid (III), which by condensation with 2-bromopyridine (IV) by means of butyllithium in ethyl ether yields 2-trifluoromethyl-6-(4-trifluoromethylphenyl)4-pyridyl-2'-pyridyl ketone (V). Finally, this compound is reduced with H2 over Pt in aqueous concentrated HCl. The starting products are prepared as follows: 1) The acrylic acid (II) is obtained by condensation of maleic anhydride (VI) with 4-trifluoromethylphenylmagnesium bromide (VII) by means of ZnCl2 in refluxing ethyl ether. An alternative method is the condensation of 4-trifluoromethylacetophenone (VIII) with glyoxylic acid (IX) by means of triethylamine at 135 C. 2) The pyridinium salt (I) is prepared by bromination of 1,1,1-trifluoroacetone (X) giving 1,1,1-trifluoro-3-bromoacetone (XI), which is then condensed with pyridine.
| 【1】 La Montagne, M.P.; et al.; Antimalarials. 6. Synthesis, antimalarial activity and configurations of rracemic alpha-(2-piperidyl)-4-pyridinemethanols. J Med Chem 1974, 17, 5, 219-523. |
| 【2】 Ash, A.B.; et al. (Department of the Army); 2-Substituted phenyl-6-trifluoromethyl-4-pyridylcarbinolamines. US 3940404 . |
| 【3】 Ash, A.B.; et al. (Department of the Army); 2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials. US 3953463 . |
| 【4】 Ash, A.B.; et al. (Department of the Army); 2-Aryl-6-trifluoromethyl-4-pyridylcarbinolamine antimalarials. US 3886167 . |
| 【5】 Castaner, J.; Roberts, P.J.; WR-180,409. Drugs Fut 1978, 3, 9, 694. |
| 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) | 39908 | 1-(3,3,3-trifluoro-2-oxopropyl)pyridinium bromide | C8H7BrF3NO | 详情 | 详情 | |
| (II) | 39906 | (E)-4-oxo-4-[4-(trifluoromethyl)phenyl]-2-butenoic acid | C11H7F3O3 | 详情 | 详情 | |
| (III) | 39910 | 2-(trifluoromethyl)-6-[4-(trifluoromethyl)phenyl]isonicotinic acid | C14H7F6NO2 | 详情 | 详情 | |
| (IV) | 29052 | 2-Bromopyridine；α-bromopyridine;α-bromoazine | 109-04-6 | C5H4BrN | 详情 | 详情 |
| (V) | 39911 | 2-pyridinyl[2-(trifluoromethyl)-6-[4-(trifluoromethyl)phenyl]-4-pyridinyl]methanone | C19H10F6N2O | 详情 | 详情 | |
| (VI) | 11182 | 2,5-Furandione; Maleic anhydride | 108-31-6 | C4H2O3 | 详情 | 详情 |
| (VII) | 39311 | bromo[4-(trifluoromethyl)phenyl]magnesium | C7H4BrF3Mg | 详情 | 详情 | |
| (VIII) | 39907 | 1-[4-(trifluoromethyl)phenyl]-1-ethanone | 709-63-7 | C9H7F3O | 详情 | 详情 |
| (IX) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (X) | 35449 | 1,1,1-trifluoroacetone | 421-50-1 | C3H3F3O | 详情 | 详情 |
| (XI) | 39909 | 3-bromo-1,1,1-trifluoroacetone | 431-35-6 | C3H2BrF3O | 详情 | 详情 |