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【结 构 式】 
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【分子编号】22546 【品名】4-sulfanylphenol 【CA登记号】637-89-8 |
【 分 子 式 】C6H6OS 【 分 子 量 】126.17904 【元素组成】C 57.11% H 4.79% O 12.68% S 25.41% |
合成路线1
该中间体在本合成路线中的序号：(IV)The alkylation of succinimide (I) with 1,2-dibromoethane (II) by means of K2CO3 in refluxing butanone gives N-(2-bromoethyl)succinimide (III), which is condensed with 4-hydroxythiophenol (IV) by means of K2CO3 in refluxing ethanol to afford 4-hydroxyphenyl 2-succinimidoethyl sulfide (V). Finally, this compound is esterified with 4-guanidinobenzoyl chloride in pyridine, and treated with methanesulfonic acid in methanol.
| 【1】 Hishinuma, I.; Kawashima, H.; Kawata, T.; Miyamoto, K.; Miyazawa, S.; Nagakawa, J.; Nagaoka, J.; Nagaoka, N.; Shimomura, N.; Souda, S.; Ueda, N.; Wakabayashi, T.; Yamanaka, T. (Eisai Co., Ltd.); Guanidinobenzoic ester deriv., a process for preparing same and pharmaceutical compsns. containing same. EP 0229370; JP 1987155253; JP 1994298730; US 4801603; US 5075335 . |
| 【2】 Prous, J.; Castaner, J.; E-3123. Drugs Fut 1988, 13, 7, 613. |
| 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) | 22543 | 2,5-pyrrolidinedione | 123-56-8 | C4H5NO2 | 详情 | 详情 |
| (II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (III) | 22545 | 1-(2-bromoethyl)-2,5-pyrrolidinedione | C6H8BrNO2 | 详情 | 详情 | |
| (IV) | 22546 | 4-sulfanylphenol | 637-89-8 | C6H6OS | 详情 | 详情 |
| (V) | 22547 | 1-[2-[(4-hydroxyphenyl)sulfanyl]ethyl]-2,5-pyrrolidinedione | C12H13NO3S | 详情 | 详情 | |
| (VI) | 22548 | 4-[[amino(imino)methyl]amino]benzoyl chloride | C8H8ClN3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation of 4-hydroxythiophenol (I) with 2-(2-chloroethyl)-1-methylpyrrolidine (II) in the presence of K2CO3 in DMF afforded the title thioether, which was isolated as the hydrochloride salt.
| 【1】 El-Abdellaoul, H.; Holsenback, H.; Vernier, J.-M.; et al.; 4-[[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A): A novel cognitive enhance with selectivity for neuronal nicotinic acetylcholine receptors. J Med Chem 1999, 42, 10, 1684. |
| 【2】 Vernier, J.M.; McDonald, I.A. (SIBIA Neurosciences, Inc.); Novel substd. aryl cpds. useful as modulators of acetylcholine receptors. EP 0874818; JP 2000501080; WO 9719059 . |
合成路线3
该中间体在本合成路线中的序号：(I)The protected acid chloride (X) was prepared by several methods. Alkylation of 4-mercaptophenol (I) with propargyl bromide (II) gave thioether (III). The phenolic hydroxyl of (III) was subsequently protected as the sulfonate ester (IV) by treatment with benzenesulfonyl chloride. The sulfide group of (IV) was then oxidized to the sulfoxide (V) by means of in situ generated performic acid. Rearrangement of the propargyl sulfoxide (V) in refluxing DME gave rise to the 3-(hydroxymethyl)benzothiophene (VI). Oxidation of alcohol (VI) to the corresponding aldehyde (VII) by means of NaOCl in the presence of TEMPO, followed by oxidation with sodium chlorite, furnished the carboxylic acid (VIII). Alternatively, the sulfonate acid (VIII) was obtained by acylation of the known 5-hydroxybenzothiophene-3-carboxylic acid (IX) with benzenesulfonyl chloride. Conversion of acid (VIII) into acid chloride (X) was effected by chlorination with SOCl2 in the presence of a catalytic amount of DMF.
| 【1】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 . |
| 【2】 Okada, T.; Honma, T.; Kakinuma, M.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Process for producing benzothiophenecarboxylic acid amide derivs.. EP 1069123; WO 9950261 . |
| 【3】 Hiramatsu, Y.; Honma, T. (Shionogi & Co. Ltd.); Process for producing 5-hydroxybenzo[b]thiophene-3-carboxylic acid derivs.. EP 1069122; WO 9950260 . |
| 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) | 22546 | 4-sulfanylphenol | 637-89-8 | C6H6OS | 详情 | 详情 |
| (II) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (III) | 60664 | 4-(2-propynylsulfanyl)phenol | C9H8OS | 详情 | 详情 | |
| (IV) | 60655 | (2S)-2-methyl-5-((2R,3S)-2-methyl-3-{(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl}oxiranyl)pentyl triethylsilyl ether; 2-methyl-4-{(E,3S)-2-methyl-4-((2S,3R)-3-methyl-3-{(4S)-4-methyl-5-[(triethylsilyl)oxy]pentyl}oxiranyl)-3-[(triethylsilyl)oxy]-1-butenyl}-1,3-thiazole | C30H57NO3SSi2 | 详情 | 详情 | |
| (V) | 60666 | 4-(2-propynylsulfinyl)phenyl benzenesulfonate | C15H12O4S2 | 详情 | 详情 | |
| (VI) | 60667 | 3-(hydroxymethyl)-1-benzothiophen-5-yl benzenesulfonate | C15H12O4S2 | 详情 | 详情 | |
| (VII) | 60668 | 3-formyl-1-benzothiophen-5-yl benzenesulfonate | C15H10O4S2 | 详情 | 详情 | |
| (VIII) | 52696 | 5-[(phenylsulfonyl)oxy]-1-benzothiophene-3-carboxylic acid | C15H10O5S2 | 详情 | 详情 | |
| (IX) | 52240 | 5-hydroxy-1-benzothiophene-3-carboxylic acid | C9H6O3S | 详情 | 详情 | |
| (X) | 52252 | 3-(chlorocarbonyl)-1-benzothiophen-5-yl benzenesulfonate | C15H9ClO4S2 | 详情 | 详情 |