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【结 构 式】 
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【分子编号】12993 【品名】1-(4,4-Dimethyl-3,4-dihydro-2H-thiochromen-6-yl)-1-ethanone 【CA登记号】 |
【 分 子 式 】C13H16OS 【 分 子 量 】220.33544 【元素组成】C 70.87% H 7.32% O 7.26% S 14.55% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of thiophenol (II) with 3-methyl-2-butenyl bromide (I) by means of NaOH in refluxing acetone gives 3-methyl-2-butenyl(phenyl)sulfide (III), which is cyclized by means of P2O5 and H3PO4 in refluxing benzene to yield 4,4-dimethyl-3,4-dihydro-1H-1-benzothiopyran (IV). The acylation of (IV) with acetyl chloride catalyzed by SnCl4 in benzene affords the corresponding 6-acetyl derivative (V), which by dehydration with lithium diisopropylamide and diethyl chlorophosphate in THF is converted into 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran (VI). Finally, this compound is condensed with ethyl 6-chloropyridine-3-carboxylate (VII) by means of butyllithium in THF. The ester (VII) is obtained by esterification of the corresponding acid (VIII) with ethanol by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP).
| 【1】 Ngo, J.; Leeson, P.A.; Castaner, J.; Tazarotene. Drugs Fut 1997, 22, 3, 249. |
| 【2】 Chandraratna, R.A.S. (Allergan, Inc.); Disubstd. acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity. EP 0284288; JP 88255277; JP 95324085 . |
| 【3】 Chandraratna, R.A.S. (Allergan, Inc.); Disubstd. acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity. US 5089509 . |
| 【4】 Chandraratna, R.A. (Allergan, Inc.); Disubstd. acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity. WO 9611686 . |
| 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) | 12989 | 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene | 870-63-3 | C5H9Br | 详情 | 详情 |
| (II) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (III) | 12991 | 1-[(3-Methyl-2-butenyl)sulfanyl]benzene; 3-Methyl-2-butenyl phenyl sulfide | C11H14S | 详情 | 详情 | |
| (IV) | 12992 | 4,4-Dimethylthiochromane | C11H14S | 详情 | 详情 | |
| (V) | 12993 | 1-(4,4-Dimethyl-3,4-dihydro-2H-thiochromen-6-yl)-1-ethanone | C13H16OS | 详情 | 详情 | |
| (VI) | 12994 | 6-Ethynyl-4,4-dimethylthiochromane | C13H14S | 详情 | 详情 | |
| (VII) | 12995 | ethyl 6-chloronicotinate | 49608-01-7 | C8H8ClNO2 | 详情 | 详情 |
| (VIII) | 12996 | 6-Chloronicotinic acid | 5326-23-8 | C6H4ClNO2 | 详情 | 详情 |