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【结 构 式】 
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【分子编号】52893 【品名】1-benzoyl-4-piperidinecarbonyl chloride 【CA登记号】 |
【 分 子 式 】C13H14ClNO2 【 分 子 量 】251.7124 【元素组成】C 62.03% H 5.61% Cl 14.08% N 5.56% O 12.71% |
合成路线1
该中间体在本合成路线中的序号：(II)N-Benzoylisonipecotic acid (I) was chlorinated with SOCl2 to produce the corresponding acid chloride (II). Acylation of the lithium enolate of (4-methoxyphenyl)acetone (III) with acid chloride (II) provided a mixture of diketone regioisomers (IV) and (V); these were separated by column chromatography. The desired diketone (IV) was then cyclized with guanidine (VI) in hot pyridine to afford the pyrimidine (VII). Basic hydrolysis of the benzamide function of (VII) gave the piperidine derivative (VIII). The target amide was finally prepared by acylation of (VIII) with 3,4-methylenedioxybenzoic acid (IX) in the presence of EDC.
| 【1】 Kawakami, H.; Kurimoto, A.; Murata, S.; Fujita, H.; Iwai, K.; Fujiwara, N.; Synthesis and bioactivities of novel piperidylpyrimidine derivatives: Inhibitors of tumor necrosis factor-alpha production. Bioorg Med Chem Lett 2000, 10, 12, 1317. |
| 【2】 Fujiwara, N.; Ueda, Y.; Murata, S.; Hirota, F.; Kawakami, H.; Fujita, H. (Sumitomo Pharmaceuticals Co., Ltd.); Piperidinylpyramidine derivs.. EP 0892795; JP 2001511764; US 5948786; WO 9738992 . |
| 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) | 52892 | 1-benzoyl-4-piperidinecarboxylic acid | C13H15NO3 | 详情 | 详情 | |
| (II) | 52893 | 1-benzoyl-4-piperidinecarbonyl chloride | C13H14ClNO2 | 详情 | 详情 | |
| (III) | 10038 | 4-Methoxyphenylacetone; 1-(4-Methoxyphenyl)acetone | 122-84-9 | C10H12O2 | 详情 | 详情 |
| (IV) | 52894 | 1-(1-benzoyl-4-piperidinyl)-4-(4-methoxyphenyl)-1,3-butanedione | C23H25NO4 | 详情 | 详情 | |
| (V) | 52895 | 1-(1-benzoyl-4-piperidinyl)-2-(4-methoxyphenyl)-1,3-butanedione | C23H25NO4 | 详情 | 详情 | |
| (VI) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (VII) | 52896 | {4-[2-amino-6-(4-methoxybenzyl)-4-pyrimidinyl]-1-piperidinyl}(phenyl)methanone | C24H26N4O2 | 详情 | 详情 | |
| (VIII) | 52897 | 4-(4-methoxybenzyl)-6-(4-piperidinyl)-2-pyrimidinamine; 4-(4-methoxybenzyl)-6-(4-piperidinyl)-2-pyrimidinylamine | C17H22N4O | 详情 | 详情 | |
| (IX) | 10125 | 1,3-Benzodioxole-5-carboxylic acid | 94-53-1 | C8H6O4 | 详情 | 详情 |