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【结 构 式】 
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【分子编号】27027 【品名】1-(ethoxymethyl)-6-[hydroxy(phenyl)methyl]-5-isopropyl-2,4(1H,3H)-pyrimidinedione 【CA登记号】 |
【 分 子 式 】C17H22N2O4 【 分 子 量 】318.37276 【元素组成】C 64.13% H 6.97% N 8.8% O 20.1% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of the silylated 5-isopropylpyrimidine (I) with chloromethyl ethyl ether (II) by means of KI in dichloromethane gives 1-(ethoxymethyl)-5-isopropyl-2-thiouracil (III), which is condensed with benzaldehyde (IV) by means of lithium diisopropylamide (LDA) in THF, and desulfurized by reaction with H2O2 and NaOH in water to afford 1-(ethoxymethyl)-5-isopropyl-6-(alpha-hydroxybenzyl)uracil (V). The reaction of (V) with acetic anhydride and pyridine gives the acetate (VI), which is finally submitted to hydrogenolysis with H2 over Pd/C in acetic acid/water/dioxane.
| 【1】 Walker, R.T.; Baba, M.; De Clerq, E.; Takashima, H.; Inouye, N.; Ubasawa, M.; Miyasaka, T.; Sekiya, K.; Shigeta, S.; Tanaka, H.; Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents. J Med Chem 1995, 38, 15, 2860. |
| 【2】 Ubasawa, M.; Tanaka, H.; Walker, R.T.; Yuasa, S.; Miyasaka, T.; De Clerq, E.; Baba, M.; HEPT derivatives: 6-benzyl-1-ethoxymethyl-5-isopropyluracil (MKC-442). Nucleosides Nucleotides 1995, 14, 3-5, 575. |
| 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) | 27025 | 5-isopropyl-4-[(trimethylsilyl)methyl]-2-[(trimethylsilyl)sulfanyl]pyrimidine | C14H28N2SSi2 | 详情 | 详情 | |
| (II) | 13149 | 1-(Chloromethoxy)ethane; Chloromethyl ethyl ether | 3188-13-4 | C3H7ClO | 详情 | 详情 |
| (III) | 27026 | 1-(ethoxymethyl)-5-isopropyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C10H16N2O2S | 详情 | 详情 | |
| (IV) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (V) | 27027 | 1-(ethoxymethyl)-6-[hydroxy(phenyl)methyl]-5-isopropyl-2,4(1H,3H)-pyrimidinedione | C17H22N2O4 | 详情 | 详情 | |
| (VI) | 27028 | [3-(ethoxymethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinyl](phenyl)methyl acetate | C19H24N2O5 | 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 reaction of 5-isopropyluracil (VII) with chloromethyl ethyl ether (II) by means of bis(trimethylsilyl)acetamide (BSA) and tetrabutylammonium iodide (TBI) in dichloromethane gives 1-(ethoxy-methyl)-5-isopropyluracil (VIII)(3), which is then condensed with benzaldehyde (IV) by means of LDA in THF to afford 1-(ethoxymethyl)-5-isopropyl-6-(alpha-hydroxybenzyl)uracil (V), already obtained.
| 【1】 Ubasawa, M.; Yuasa, S. (Mitsubishi Chemical Corp.); Antiviral combinations of 2',3'-dideoxyribonucleosides with 6-benzyl-1-ethoxymethyl-5-substd. uracil derivs.. EP 0631783; JP 1995097324 . |
| 【2】 Ubasawa, M.; et al. (Mitsubishi Chemical Corp.); Production of 6-aralkyl substituted pyrimidine derivative. JP 1996003143 . |
| 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) | 27029 | trimethylsilyl 4-[(trimethylsilyl)methyl]-2-pyrimidinyl sulfide | C11H22N2SSi2 | 详情 | 详情 | |
| (II) | 13149 | 1-(Chloromethoxy)ethane; Chloromethyl ethyl ether | 3188-13-4 | C3H7ClO | 详情 | 详情 |
| (IV) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (V) | 27027 | 1-(ethoxymethyl)-6-[hydroxy(phenyl)methyl]-5-isopropyl-2,4(1H,3H)-pyrimidinedione | C17H22N2O4 | 详情 | 详情 | |
| (VI) | 27028 | [3-(ethoxymethyl)-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinyl](phenyl)methyl acetate | C19H24N2O5 | 详情 | 详情 | |
| (VII) | 27030 | 5-isopropyl-2,4(1H,3H)-pyrimidinedione | C7H10N2O2 | 详情 | 详情 | |
| (VIII) | 27031 | 1-(ethoxymethyl)-5-isopropyl-2,4(1H,3H)-pyrimidinedione | C10H16N2O3 | 详情 | 详情 |