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【结 构 式】 
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【分子编号】49921 【品名】ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate 【CA登记号】 |
【 分 子 式 】C19H19BrClNO4S 【 分 子 量 】472.7869 【元素组成】C 48.27% H 4.05% Br 16.9% Cl 7.5% N 2.96% O 13.54% S 6.78% |
合成路线1
该中间体在本合成路线中的序号：(V)Bromination of the coumarin derivative (I) with Br2 in DMF afforded the bromo coumarin (II). Diels-Alder cycloaddition between bromo coumarin (II) and ethyl 3-(trimethylsilyl)propiolate (III) with concomitant decarboxylation furnished the tetrahydronaphthalene (IV). After desilylation of (IV) with trifluoroacetic acid, the resultant ester (V) was reduced to alcohol (VI) using the combination LiAlH4-AlCl3. Further oxidation of the alcohol function of (VI) to aldehyde (VII) was performed with 4-benzylpyridinium dichromate (BPDC) in CH2Cl2. Wittig reaction of aldehyde (VII) with methyl (triphenylphosphoranylidene)acetate produced the arylacrylate ester (VIII), which was then reduced to the saturated ester (IX) employing NaBH4 in the presence of CoCl2.
| 【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57. |
| 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) | 19586 | 4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide | C15H14ClNO4S | 详情 | 详情 | |
| (II) | 19587 | N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide | C15H13BrClNO4S | 详情 | 详情 | |
| (III) | 23898 | ethyl 3-(trimethylsilyl)-2-propynoate | 29394-58-9 | C8H14O2Si | 详情 | 详情 |
| (IV) | 49920 | ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate | C22H27BrClNO4SSi | 详情 | 详情 | |
| (V) | 49921 | ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate | C19H19BrClNO4S | 详情 | 详情 | |
| (VI) | 19590 | N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide | C17H17BrClNO3S | 详情 | 详情 | |
| (VII) | 19591 | N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide | C17H15BrClNO3S | 详情 | 详情 | |
| (VIII) | 49922 | methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate | C20H19BrClNO4S | 详情 | 详情 | |
| (IX) | 49923 | methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate | C20H21BrClNO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Bromination of the coumarin derivative (I) with Br2 in DMF afforded the bromo coumarin (II). Diels-Alder cycloaddition between bromo coumarin (II) and ethyl 3-(trimethylsilyl)propiolate (III) with concomitant decarboxylation furnished the tetrahydronaphthalene (IV). After desilylation of (IV) with trifluoroacetic acid, the resultant ester (V) was reduced to alcohol (VI) using the combination LiAlH4-AlCl3. Further oxidation of the alcohol function of (VI) to aldehyde (VII) was performed with 4-benzylpyridinium dichromate (BPDC) in CH2Cl2. Wittig reaction of aldehyde (VII) with methyl (triphenylphosphoranylidene)acetate produced the arylacrylate ester (VIII), which was then reduced to the saturated ester (IX) employing NaBH4 in the presence of CoCl2.
| 【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57. |
| 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) | 19586 | 4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide | C15H14ClNO4S | 详情 | 详情 | |
| (II) | 19587 | N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide | C15H13BrClNO4S | 详情 | 详情 | |
| (III) | 23898 | ethyl 3-(trimethylsilyl)-2-propynoate | 29394-58-9 | C8H14O2Si | 详情 | 详情 |
| (IV) | 49920 | ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate | C22H27BrClNO4SSi | 详情 | 详情 | |
| (V) | 49921 | ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate | C19H19BrClNO4S | 详情 | 详情 | |
| (VI) | 19590 | N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide | C17H17BrClNO3S | 详情 | 详情 | |
| (VII) | 19591 | N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide | C17H15BrClNO3S | 详情 | 详情 | |
| (VIII) | 49922 | methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate | C20H19BrClNO4S | 详情 | 详情 | |
| (IX) | 49923 | methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate | C20H21BrClNO4S | 详情 | 详情 |