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【结 构 式】 
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【分子编号】10360 【品名】3,4-Dimethylumbelliferone; 7-Hydroxy-3,4-dimethyl-2H-chromen-2-one 【CA登记号】2107-78-0 |
【 分 子 式 】C11H10O3 【 分 子 量 】190.1986 【元素组成】C 69.46% H 5.3% O 25.24% |
合成路线1
该中间体在本合成路线中的序号：(VI)The total synthesis of picumast dihydrochloride has been described: The alkylation of piperazine (I) with 4-chlorobenzyl chloride (II) in ethanol gives 1-(4-chlorobenzyl)piperazine (III), which is alkylated again with 1-bromo-3-chloropropane (IV) by means of triethylamine in a suitable solvent to yield 1-(4-chlorobenzyl)-4-(3-chloropropyl)piperazine (V). Finally, this compound is condensed with 7-hydroxy-3,4-dimethylcoumarin (VI) by means of K2CO3 in refluxing butanone. Compound (VI) is obtained by cyclization of resorcinol (VII) with ethyl 2-methylacetoacetate (VIII) by means of refluxing acetic acid containing HCl.
| 【1】 Witte, E.-C.; Chemical synthesis of picumast dihydrochloride. Arzneim-Forsch Drug Res 1989, 39, 10a, 1309. |
| 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) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (II) | 10356 | 1-Chloro-4-(chloromethyl)benzene; 4-Chlorobenzyl chloride | 104-83-6 | C7H6Cl2 | 详情 | 详情 |
| (III) | 10357 | 1-(4-Chlorobenzyl)piperazine; N-(4-Chlorobenzyl)piperazine | C11H15ClN2 | 详情 | 详情 | |
| (IV) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (V) | 10359 | 1-(4-Chlorobenzyl)-4-(3-chloropropyl)piperazine | C14H20Cl2N2 | 详情 | 详情 | |
| (VI) | 10360 | 3,4-Dimethylumbelliferone; 7-Hydroxy-3,4-dimethyl-2H-chromen-2-one | 2107-78-0 | C11H10O3 | 详情 | 详情 |
| (VII) | 10361 | 1,3-Dihydroxybenzene; m-Dihydroxybenzene; Resorcinol; Resorcin; 1,3-Benzenediol | 108-46-3 | C6H6O2 | 详情 | 详情 |
| (VIII) | 10362 | ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate | 609-14-3 | C7H12O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)By condensation of 7-hydroxy-3,4-dimethylcoumarin (I) with 1-(3-chloropropyl)-4-(4-chlorobenzyl)piperazine (II) by means of K2CO3 and KI in refluxing butanone.
| 【1】 Witte, E.C.; et al. (Boehringer Ingelheim GmbH); Coumarin-7-yloxyalkyl piperazine compounds. DE 2123924; FR 2137731; GB 1335946; JP 58219176; US 3810898 . |
| 【2】 Hillier, K.; Castaner, J.; BM-15100. Drugs Fut 1977, 2, 7, 438. |
合成路线3
该中间体在本合成路线中的序号：(III)Pechmann condensation of resorcinol (I) with ethyl 2-methylacetylacetate (II) in concentrated sulfuric acid at room temperature provided coumarine (III). Further treatment with one equivalent of sodium hydride and an excess of sulfamoyl chloride yielded the target sulfamate.
| 【1】 Woo, L.W.C.; et al.; Steroidal and nonsteroidal sulfamates as potent inhibitors of steroid sulfatase. J Med Chem 1998, 41, 7, 1068. |
| 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) | 10361 | 1,3-Dihydroxybenzene; m-Dihydroxybenzene; Resorcinol; Resorcin; 1,3-Benzenediol | 108-46-3 | C6H6O2 | 详情 | 详情 |
| (II) | 10362 | ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate | 609-14-3 | C7H12O3 | 详情 | 详情 |
| (III) | 10360 | 3,4-Dimethylumbelliferone; 7-Hydroxy-3,4-dimethyl-2H-chromen-2-one | 2107-78-0 | C11H10O3 | 详情 | 详情 |