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【结 构 式】 
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【分子编号】18317 【品名】ethyl 2-[6-[4-(acetoxy)phenyl]-5-methyl-1-[2-(methylsulfanyl)benzyl]-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate 【CA登记号】 |
【 分 子 式 】C27H26N2O6S2 【 分 子 量 】538.64532 【元素组成】C 60.21% H 4.87% N 5.2% O 17.82% S 11.91% |
合成路线1
该中间体在本合成路线中的序号：(IX)Thiophene (III) was obtained by condensation of (4-methoxyphenyl)acetone (I) with ethyl cyanoacetate (II) in the presence of NH4OAc and AcOH, followed by treatment with sulfur and diethylamine. Subsequent reaction of (III) with ethyl isocyanato-acetate (IV) in pyridine at 45 C and further cyclization with ethanolic NaOEt provided the thienopyrimidine (V). Cleavage of the methyl ether was performed by treatment with AlCl3 and dimethyl disulfide in CH2Cl2 at r.t. to afford phenol (VI), which was then acetylated with Ac2O in pyridine to give ester (VII). N-Alkylation with 2-(methylsulfanyl)benzyl chloride (VIII) in the presence of K2CO3 in DMF yielded (IX), and then the acetate ester was hydrolyzed with K2CO3 in a mixture of H2O/MeOH/THF. The resulting phenol (X) was alkylated with chloromethyl methyl ether (XI) in the presence of NaH to provide (XII).
| 【1】 Cho, N.; Nara, Y.; Harada, M.; Sugo, T.; Masuda, Y.; Abe, A.; Kusumoto, K.; Itoh, Y.; Ohtaki, T.; Watanabe, T.; Furuya, S.; Thieno[2,3-d]pyrimidine-3-acetic acids a new class of nonpeptide endothelin receptor antagonists. Chem Pharm Bull 1998, 46, 11, 1724. |
| 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) | 10038 | 4-Methoxyphenylacetone; 1-(4-Methoxyphenyl)acetone | 122-84-9 | C10H12O2 | 详情 | 详情 |
| (II) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (III) | 18311 | ethyl 2-amino-5-(4-methoxyphenyl)-4-methyl-3-thiophenecarboxylate | C15H17NO3S | 详情 | 详情 | |
| (IV) | 18312 | ETHYL ISOCYANATOACETATE; ethyl 2-isocyanatoacetate | 2949-22-6 | C5H7NO3 | 详情 | 详情 |
| (V) | 18313 | ethyl 2-[6-(4-methoxyphenyl)-5-methyl-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C18H18N2O5S | 详情 | 详情 | |
| (VI) | 18314 | ethyl 2-[6-(4-hydroxyphenyl)-5-methyl-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C17H16N2O5S | 详情 | 详情 | |
| (VII) | 18315 | ethyl 2-[6-[4-(acetoxy)phenyl]-5-methyl-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C19H18N2O6S | 详情 | 详情 | |
| (VIII) | 18316 | 1-(chloromethyl)-2-(methylsulfanyl)benzene; 2-(chloromethyl)phenyl methyl sulfide | C8H9ClS | 详情 | 详情 | |
| (IX) | 18317 | ethyl 2-[6-[4-(acetoxy)phenyl]-5-methyl-1-[2-(methylsulfanyl)benzyl]-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C27H26N2O6S2 | 详情 | 详情 | |
| (X) | 18318 | ethyl 2-[6-(4-hydroxyphenyl)-5-methyl-1-[2-(methylsulfanyl)benzyl]-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C25H24N2O5S2 | 详情 | 详情 | |
| (XI) | 18319 | Chloro(methoxy)methane; Chloromethyl methyl ether | 107-30-2 | C2H5ClO | 详情 | 详情 |
| (XII) | 18320 | ethyl 2-[6-[4-(methoxymethoxy)phenyl]-5-methyl-1-[2-(methylsulfanyl)benzyl]-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl]acetate | C27H28N2O6S2 | 详情 | 详情 |