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【结 构 式】 
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【分子编号】28332 【品名】3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-5-oxopentanoic acid 【CA登记号】 |
【 分 子 式 】C21H26O3S 【 分 子 量 】358.50164 【元素组成】C 70.36% H 7.31% O 13.39% S 8.94% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 3-(4-methylphenyl)propionic acid (I) with SOCl2 gives the corresponding acyl chloride (II), which is condensed with thiophene (III) by means SnCl4 yielding 3-(4-methylphenyl)-1-(2-thienyl)propan-1-one (IV). The reduction of (IV) with hydrazine and KOH in hot triethylene glycol affords 2-[3-(4-methylphenyl)propyl]thiophene (V), which is condensed with 3,3-dimethyl glutaric anhydride (VI), by means of AlCl3 in hot nitrobenzene giving the 5-oxopentanoic acid derivative (VII). The reduction of (VII) with hydrazine and KOH as before yields the pentanoic acid derivative (VIII), which is condensed with 4-(2,3,4-trimethoxybenzyl)piperazine (IX) by means of oxalyl chloride to afford the acyl piperazine (X). Finally, the amide group of (X) is reduced with LiAlH4 in ethyl ether.
| 【1】 Wierzbicki, M.; et al.; Amino derivatives of phenyl alkyl thiophene as inhibitors of bone resorption. Structure-activity relationship. Arzneim-Forsch Drug Res 1998, 48, 8, 840. |
| 【2】 Wierzbicki, M.; Sauveur, F.; Bonnet, J.; Brisset, M.; Tordjman, C. (ADIR et Cie.); Thiophene derivs., process for their preparation and pharmaceutical compsns. containing them. AU 9166901; EP 0429370; FR 2655043; JP 1991190872; US 5061704 . |
| 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) | 28328 | 3-(4-methylphenyl)propionic acid | 1505-50-6 | C10H12O2 | 详情 | 详情 |
| (II) | 28329 | 3-(4-methylphenyl)propanoyl chloride | C10H11ClO | 详情 | 详情 | |
| (III) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (IV) | 28330 | 3-(4-methylphenyl)-1-(2-thienyl)-1-propanone | C14H14OS | 详情 | 详情 | |
| (V) | 28331 | 2-[3-(4-methylphenyl)propyl]thiophene | C14H16S | 详情 | 详情 | |
| (VI) | 25549 | 4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione | 4160-82-1 | C7H10O3 | 详情 | 详情 |
| (VII) | 28332 | 3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-5-oxopentanoic acid | C21H26O3S | 详情 | 详情 | |
| (VIII) | 28333 | 3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]pentanoic acid | C21H28O2S | 详情 | 详情 | |
| (IX) | 24354 | 2,3-dimethoxy-4-(1-piperazinylmethyl)phenyl methyl ether | C14H22N2O3 | 详情 | 详情 | |
| (X) | 28334 | 3,3-dimethyl-5-[5-[3-(4-methylphenyl)propyl]-2-thienyl]-1-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]-1-pentanone | C35H48N2O4S | 详情 | 详情 |