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【结 构 式】 
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【药物名称】 【化学名称】2-(Cyclohexylsulfanyl)-6-[1-(2,6-difluorophenyl)ethyl]-5-methylpyrimidin-4(3H)-one 【CA登记号】 【 分 子 式 】C19H22F2N2OS 【 分 子 量 】364.46079 |
【开发单位】 【药理作用】 |
合成路线1
The alkylation of 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (I) with cyclohexyl chloride (II) by means of K2CO3 gives 2-(cyclohexylsulfanyl)-6-(2,6-difluorobenzyl)-5-methylpyridmidin-4(3H)-one (III), which is then methylated with Me-Cl and LDA in THF/HMPA to yield the target alpha-methylbenzyl pyrimidinone.
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51815 | 6-(2,6-difluorobenzyl)-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H10F2N2OS | 详情 | 详情 | |
| (II) | 51795 | chlorocyclohexane; Hexahydrochlorobenzene; Cyclohexyl chloride | 542-18-7 | C6H11Cl | 详情 | 详情 |
| (III) | 51826 | 2-(cyclohexylsulfanyl)-6-(2,6-difluorobenzyl)-5-methyl-4(3H)-pyrimidinone | C18H20F2N2OS | 详情 | 详情 |
合成路线2
The methylation of 2-(2,6-difluorophenyl)acetic acid (I) with Me-Cl and LDA in THF/HMPA gives 2-(2,6-difluorophenyl)propionic acid (II), which is condensed with 2-methylmalonic acid monoethyl ester potassium salt (III) to yield 4´(2,6-difluorophenyl)-2-methyl-3-oxopentanoic acid (IV). The cyclization of (IV) with thiourea (V) affords 6-[1-(2,6-difluorophenyl)ethyl]-5-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (VI), which is finally alkylated with cyclohexyl chloride (VII) to provide the target pyrimidinone derivative.
| 【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159. |
| 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) | 51809 | 2,6-Difluorophenylacetic acid | 85068-28-6 | C8H6F2O2 | 详情 | 详情 |
| (II) | 51820 | 2-(2,6-difluorophenyl)propionic acid | C9H8F2O2 | 详情 | 详情 | |
| (III) | 51813 | potassium 3-ethoxy-2-methyl-3-oxopropanoate | C6H9KO4 | 详情 | 详情 | |
| (IV) | 51821 | ethyl 4-(2,6-difluorophenyl)-2-methyl-3-oxopentanoate | C14H16F2O3 | 详情 | 详情 | |
| (V) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VI) | 51822 | 6-[1-(2,6-difluorophenyl)ethyl]-5-methyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C13H12F2N2OS | 详情 | 详情 | |
| (VII) | 51795 | chlorocyclohexane; Hexahydrochlorobenzene; Cyclohexyl chloride | 542-18-7 | C6H11Cl | 详情 | 详情 |