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【结 构 式】 
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【分子编号】27032 【品名】2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate 【CA登记号】609-12-1 |
【 分 子 式 】C7H13BrO2 【 分 子 量 】209.08302 【元素组成】C 40.21% H 6.27% Br 38.22% O 15.3% |
合成路线1
该中间体在本合成路线中的序号：(IX)The condensation of ethyl 2-bromo-3-methylbutyrate (IX) with phenylacetonitrile (X) by means of activated Zn in THF gives the ethyl 2-isopropyl-3-oxo-4-phenylbutyrate (XI), which is cyclized with thiourea (XII) by means of sodium ethoxide in refluxing ethanol yielding 6-benzyl-5-isopropyl-2-thioracil (XIII). The desulfurization of (XIII) with a refluxing solution of 10% chloroacetic acid in water affords the corresponding uracil (XIV), which is finally alkylated with chloromethyl ethyl ether (II) and BSA in chloroform.
| 【1】 Larsen, D.K.; et al.; Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. J Med Chem 1996, 39, 12, 2427. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 13149 | 1-(Chloromethoxy)ethane; Chloromethyl ethyl ether | 3188-13-4 | C3H7ClO | 详情 | 详情 |
| (IX) | 27032 | 2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate | 609-12-1 | C7H13BrO2 | 详情 | 详情 |
| (X) | 17046 | Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide | 140-29-4 | C8H7N | 详情 | 详情 |
| (XI) | 27033 | ethyl 2-isopropyl-3-oxo-4-phenylbutanoate | C15H20O3 | 详情 | 详情 | |
| (XII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (XIII) | 27034 | 6-benzyl-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C14H16N2OS | 详情 | 详情 | |
| (XIV) | 27035 | 6-benzyl-5-isopropyl-2,4(1H,3H)-pyrimidinedione | C14H16N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of 2-phenylacetonitrile (I) with 2-bromo-3-methylbutyric acid ethyl ester (II) by means of Zn in THF gives the ketoester (III), which is cyclized with thiourea (IV) by means of sodium ethoxide in ethanol yielding 6-benzyl-5-isopropyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one (V). Finally, this compound is treated with chloromethyl methyl sulfide (VI) and K2CO3 in DMF.
| 【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; 5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series. Bioorg Med Chem Lett 1998, 8, 12, 1461. |
| 【2】 Sudbeck, E.A.; Mao, C.; Vig, R.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Uckun, F.M.; Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 1998, 42, 12, 3225. |
| 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) | 17046 | Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide | 140-29-4 | C8H7N | 详情 | 详情 |
| (II) | 27032 | 2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate | 609-12-1 | C7H13BrO2 | 详情 | 详情 |
| (III) | 27033 | ethyl 2-isopropyl-3-oxo-4-phenylbutanoate | C15H20O3 | 详情 | 详情 | |
| (IV) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (V) | 27034 | 6-benzyl-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C14H16N2OS | 详情 | 详情 | |
| (VI) | 27701 | chloro(methylsulfanyl)methane | 2373-51-5 | C2H5ClS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of 2-(3,5-dimethylphenyl)acetonitrile (I) with ethyl 2-bromo-3-methylbutyrate (II) by means of Zn in THF gives the beta-ketoester (III), which is cyclized with thiourea (IV) by means of sodium ethoxide in ethanol yielding the thioxopyrimidinone (V). Finally, this compound is condensed with choromethyl methyl sulfide by means of K2CO3 in DMF.
| 【1】 Vig, R.; Mao, C.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Sudbeck, E.A.; Uckun, F.M.; 5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series. Bioorg Med Chem Lett 1998, 8, 12, 1461. |
| 【2】 Sudbeck, E.A.; Mao, C.; Vig, R.; Venkatachalam, T.K.; Tuel-Ahlgren, L.; Uckun, F.M.; Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 1998, 42, 12, 3225. |
| 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) | 30213 | 2-(3,5-dimethylphenyl)acetonitrile | 39101-54-7 | C10H11N | 详情 | 详情 |
| (II) | 27032 | 2-Bromoisovalerianic acid ethyl ester; ethyl 2-bromo-3-methylbutanoate | 609-12-1 | C7H13BrO2 | 详情 | 详情 |
| (III) | 30214 | ethyl 4-(3,5-dimethylphenyl)-2-isopropyl-3-oxobutanoate | C17H24O3 | 详情 | 详情 | |
| (IV) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (V) | 30215 | 6-(3,5-dimethylbenzyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C16H20N2OS | 详情 | 详情 | |
| (VI) | 27701 | chloro(methylsulfanyl)methane | 2373-51-5 | C2H5ClS | 详情 | 详情 |