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【结 构 式】 
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【分子编号】45654 【品名】3-chloro-5-[4-(trifluoromethyl)phenoxy]isonicotinaldehyde 【CA登记号】 |
【 分 子 式 】C13H7ClF3NO2 【 分 子 量 】301.6520296 【元素组成】C 51.76% H 2.34% Cl 11.75% F 18.89% N 4.64% O 10.61% |
合成路线1
该中间体在本合成路线中的序号：(IV)Lithiation of 3,5-dichloropyridine (I) using LDA in cold THF, followed by treatment with methyl formate, furnished aldehyde (II). Subsequent reaction of (II) with the potassium salt of 4-(trifluoromethyl)phenol (III) provided the diaryl ether (IV). Without isolation, (IV) was further condensed with methyl thioglycolate (V) in the presence of Cs2CO3, yielding the thienopyridine (VI). The title amide was then obtained by displacement of the methyl ester of (VI) with methylamine in the presence of NaH. Alternatively, ester (VI) was first hydrolyzed to acid (VII) and then condensed with methylamine employing EDC and HOBt.
| 【1】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)theino[2,3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 2001, 44, 21, 3469. |
| 【2】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells: Aryl modification of 4-aryloxy thieno[2,3-C]pyridines. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 145. |
| 【3】 Lartey, K.; Gunawardana, I.W.; Stout, D.M.; Bhatia, P.; Patel, M.V.; Staeger, M.A.; Boyd, S.A.; Mort, N.A.; Zhu, G.-D.; McCarty, C.M.; Stewart, A.O.; Arendsen, D.L.; Condroski, K.R.; Freeman, J.C. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory cpds.. WO 9962908 . |
| 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) | 35535 | 3,5-dichloropyridine | 2457-47-8 | C5H3Cl2N | 详情 | 详情 |
| (II) | 35536 | 3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde | 136590-83-5 | C6H3Cl2NO | 详情 | 详情 |
| (III) | 35537 | 3-chloro-5-[(4-methylphenyl)sulfanyl]isonicotinaldehyde | C13H10ClNOS | 详情 | 详情 | |
| (IV) | 45654 | 3-chloro-5-[4-(trifluoromethyl)phenoxy]isonicotinaldehyde | C13H7ClF3NO2 | 详情 | 详情 | |
| (V) | 18838 | methyl 2-sulfanylacetate | 2365-48-2 | C3H6O2S | 详情 | 详情 |
| (VI) | 45655 | methyl 4-[4-(trifluoromethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxylate | C16H10F3NO3S | 详情 | 详情 | |
| (VII) | 45656 | 4-[4-(trifluoromethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxylic acid | C15H8F3NO3S | 详情 | 详情 |