|
【结 构 式】 
|
【分子编号】52234 【品名】sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate 【CA登记号】 |
【 分 子 式 】C17H14NNaO3 【 分 子 量 】303.292868 【元素组成】C 67.32% H 4.65% N 4.62% Na 7.58% O 15.83% |
合成路线1
该中间体在本合成路线中的序号：(XIX)In an alternative procedure, isovanillin (XI) was protected by O-benzylation, giving (XII), and its aldehyde group was subsequently reduced to alcohol (XIII) with NaBH4. The benzylic alcohol (XIII) was chlorinated to (XIV), which was converted to nitrile (XV) by chloride displacement with tetraethylammonium cyanide. Nitrile (XV) was subjected to Claisen condensation with ethyl formate, yielding (XVI), followed by sulfonylation with benzenesulfonyl chloride to afford (XVII), which was cyclized to the amino thiophene (XVIII) by treatment with ethyl thioglycolate (IV) as above. Condensation of (XVIII) with 2,5-dimethoxytetrahydrofuran (VI) produced the corresponding pyrrole derivative (XIX). After conversion of the ester group of (XIX) to amide (XX) upon heating with pyrrolidine (VIII), its cyclization with POCl3 furnished the thienopyrrolizinone (XXI). The O-benzyl protecting group of (XXI) was finally cleaved by treatment with HBr in HOAc.
| 【1】 Lisowski, V.; et al.; Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents. Bioorg Med Chem Lett 2001, 11, 16, 2205. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 18838 | methyl 2-sulfanylacetate | 2365-48-2 | C3H6O2S | 详情 | 详情 |
| (VI) | 12121 | (Z)-4-(Dimethylamino)-3-imidazo[1,2-a]pyridin-6-yl-3-buten-2-one | C13H15N3O | 详情 | 详情 | |
| (VIII) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (XI) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
| (XII) | 10966 | 3-(Benzyloxy)-4-methoxybenzaldehyde; 3-Benzyloxy-4-methoxybenzaldehyde | 6346-05-0 | C15H14O3 | 详情 | 详情 |
| (XIII) | 23823 | 5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid | C20H32O5 | 详情 | 详情 | |
| (XIV) | 52232 | benzyl 5-(chloromethyl)-2-methoxyphenyl ether; 2-(benzyloxy)-4-(chloromethyl)-1-methoxybenzene | C15H15ClO2 | 详情 | 详情 | |
| (XV) | 52233 | (3-Benzyloxy-4-methoxyphenyl)acetonitrile | C16H15NO2 | 详情 | 详情 | |
| (XVI) | 52234 | sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate | C17H14NNaO3 | 详情 | 详情 | |
| (XVII) | 52235 | (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyanoethenyl benzenesulfonate | C23H19NO5S | 详情 | 详情 | |
| (XVIII) | 52236 | methyl 3-amino-4-[3-(benzyloxy)-4-methoxyphenyl]-2-thiophenecarboxylate | C20H19NO4S | 详情 | 详情 | |
| (XIX) | 52234 | sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate | C17H14NNaO3 | 详情 | 详情 | |
| (XX) | 52238 | [4-[3-(benzyloxy)-4-methoxyphenyl]-3-(1H-pyrrol-1-yl)-2-thienyl](1-pyrrolidinyl)methanone | C27H26N2O3S | 详情 | 详情 | |
| (XXI) | 52239 | 3-[3-(benzyloxy)-4-methoxyphenyl]-8H-thieno[2,3-b]pyrrolizin-8-one | C23H17NO3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)In an alternative procedure, isovanillin (XI) was protected by O-benzylation, giving (XII), and its aldehyde group was subsequently reduced to alcohol (XIII) with NaBH4. The benzylic alcohol (XIII) was chlorinated to (XIV), which was converted to nitrile (XV) by chloride displacement with tetraethylammonium cyanide. Nitrile (XV) was subjected to Claisen condensation with ethyl formate, yielding (XVI), followed by sulfonylation with benzenesulfonyl chloride to afford (XVII), which was cyclized to the amino thiophene (XVIII) by treatment with ethyl thioglycolate (IV) as above. Condensation of (XVIII) with 2,5-dimethoxytetrahydrofuran (VI) produced the corresponding pyrrole derivative (XIX). After conversion of the ester group of (XIX) to amide (XX) upon heating with pyrrolidine (VIII), its cyclization with POCl3 furnished the thienopyrrolizinone (XXI). The O-benzyl protecting group of (XXI) was finally cleaved by treatment with HBr in HOAc.
| 【1】 Lisowski, V.; et al.; Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents. Bioorg Med Chem Lett 2001, 11, 16, 2205. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 18838 | methyl 2-sulfanylacetate | 2365-48-2 | C3H6O2S | 详情 | 详情 |
| (VI) | 12121 | (Z)-4-(Dimethylamino)-3-imidazo[1,2-a]pyridin-6-yl-3-buten-2-one | C13H15N3O | 详情 | 详情 | |
| (VIII) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (XI) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
| (XII) | 10966 | 3-(Benzyloxy)-4-methoxybenzaldehyde; 3-Benzyloxy-4-methoxybenzaldehyde | 6346-05-0 | C15H14O3 | 详情 | 详情 |
| (XIII) | 23823 | 5-[4-hydroxy-2-(3-hydroxybutyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid | C20H32O5 | 详情 | 详情 | |
| (XIV) | 52232 | benzyl 5-(chloromethyl)-2-methoxyphenyl ether; 2-(benzyloxy)-4-(chloromethyl)-1-methoxybenzene | C15H15ClO2 | 详情 | 详情 | |
| (XV) | 52233 | (3-Benzyloxy-4-methoxyphenyl)acetonitrile | C16H15NO2 | 详情 | 详情 | |
| (XVI) | 52234 | sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate | C17H14NNaO3 | 详情 | 详情 | |
| (XVII) | 52235 | (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyanoethenyl benzenesulfonate | C23H19NO5S | 详情 | 详情 | |
| (XVIII) | 52236 | methyl 3-amino-4-[3-(benzyloxy)-4-methoxyphenyl]-2-thiophenecarboxylate | C20H19NO4S | 详情 | 详情 | |
| (XIX) | 52234 | sodium (Z)-2-[3-(benzyloxy)-4-methoxyphenyl]-2-cyano-1-ethenolate | C17H14NNaO3 | 详情 | 详情 | |
| (XX) | 52238 | [4-[3-(benzyloxy)-4-methoxyphenyl]-3-(1H-pyrrol-1-yl)-2-thienyl](1-pyrrolidinyl)methanone | C27H26N2O3S | 详情 | 详情 | |
| (XXI) | 52239 | 3-[3-(benzyloxy)-4-methoxyphenyl]-8H-thieno[2,3-b]pyrrolizin-8-one | C23H17NO3S | 详情 | 详情 |