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【结 构 式】 
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【分子编号】17810 【品名】3-methyl-2-butenoyl chloride; 3,3-Dimethylacryloyl chloride 【CA登记号】3350-78-5 |
【 分 子 式 】C5H7ClO 【 分 子 量 】118.56268 【元素组成】C 50.65% H 5.95% Cl 29.9% O 13.49% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The reaction of ethyl valerimidate hydrochloride (I) with cyanamide in ethanol yielded cyanoimidate (II), which was converted into the cyanoimidoylglycine (IV) on treatment with glycine ethyl ester (III) and triethylamine. Alkylation of (IV) with the biphenyl derivative (V) in the presence of 1 mole of NaH in DMF gave the intermediate cyanoamidine (VI), which, by further addition of half an equivalent of sodium hydride was cyclized to the imidazole (VII). Acylation of (VII) with 3,3-dimethylacryloyl chloride (VIII) in cold pyridine yielded amide (IX), and then N-alkylation with iodomethane and sodium hydride in DMF provided (X). Acidic treatment with acetic acid in refluxing ethanol removed the trityl group to give (XI).
| 【1】 Okazaki, T.; et al.; Studies on nonpeptide angiotensin II receptor antagonists. IV. Synthesis and biological evaluation of 4-acrylamide-1H-imidazole derivatives. Chem Pharm Bull 1998, 46, 6, 973. |
| 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) | 15120 | ethyl pentanimidoate | C7H15NO | 详情 | 详情 | |
| (II) | 17804 | ethyl N-cyanopentanimidoate | C8H14N2O | 详情 | 详情 | |
| (III) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
| (IV) | 17806 | ethyl 2-(pentanimidoylamino)acetate | C10H17N3O2 | 详情 | 详情 | |
| (V) | 65045 | 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-trityl-1H-1,2,3,4-tetraazole | C33H25BrN4 | 详情 | 详情 | |
| (VI) | 17808 | ethyl 2-(pentanimidoyl[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amino)acetate | C43H41N7O2 | 详情 | 详情 | |
| (VII) | 17809 | ethyl 4-amino-2-butyl-1-[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate | C43H41N7O2 | 详情 | 详情 | |
| (VIII) | 17810 | 3-methyl-2-butenoyl chloride; 3,3-Dimethylacryloyl chloride | 3350-78-5 | C5H7ClO | 详情 | 详情 |
| (IX) | 17811 | ethyl 2-butyl-4-[(3-methyl-2-butenoyl)amino]-1-[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate | C48H47N7O3 | 详情 | 详情 | |
| (X) | 17812 | ethyl 2-butyl-4-[methyl(3-methyl-2-butenoyl)amino]-1-[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate | C49H49N7O3 | 详情 | 详情 | |
| (XI) | 17813 | ethyl 2-butyl-4-[methyl(3-methyl-2-butenoyl)amino]-1-[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate | C30H35N7O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Esterification of 1-naphthol (I) with 3-methylcrotonic acid chloride (II) provides ester (III), which subsequently rearranges to the hydroxy ketone (IV). Cyclization of (IV) under acidic conditions provides the tricyclic system (V). Keto group reduction in (V) by means of LiAlH4 leads to alcohol (VI), which upon acidic treatment is dehydrated to olefin (VII). Further catalytic hydrogenation of (VII) in the presence of Pd/C yields the dihydro naphthopyran (VIII). Electrophilic nitration of (VIII) provides (IX). After reduction of nitro derivative (IX) to the corresponding amine (X) by means of Sn/HCl, acylation with acetic anhydride furnishes acetamide (XI). Finally, oxidation of (XI) with concentrated nitric acid gives rise to the target ortho-quinone .
| 【1】 Amaral, A.C.F.; Barnes, R.A.; The total synthesis of beta-lapachone. J Heterocycl Chem 1992, 29, 1457. |
| 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) | 22935 | alpha-naphthol; 1-naphthol | 90-15-3 | C10H8O | 详情 | 详情 |
| (II) | 17810 | 3-methyl-2-butenoyl chloride; 3,3-Dimethylacryloyl chloride | 3350-78-5 | C5H7ClO | 详情 | 详情 |
| (III) | 60270 | 1-naphthalenyl 3-methyl-2-butenoate | C15H14O2 | 详情 | 详情 | |
| (IV) | 60271 | 1-(1-hydroxy-2-naphthalenyl)-3-methyl-2-buten-1-one | C15H14O2 | 详情 | 详情 | |
| (V) | 60272 | 2,2-dimethyl-2,3-dihydro-4H-benzo[h]chromen-4-one | C15H14O2 | 详情 | 详情 | |
| (VI) | 60273 | 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-4-ol | C15H16O2 | 详情 | 详情 | |
| (VII) | 60274 | 2,2-dimethyl-2H-benzo[h]chromene | C15H14O | 详情 | 详情 | |
| (VIII) | 60275 | 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene | C15H16O | 详情 | 详情 | |
| (IX) | 60276 | 2,2-dimethyl-6-nitro-3,4-dihydro-2H-benzo[h]chromene | C15H15NO3 | 详情 | 详情 | |
| (X) | 60277 | 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-amine; 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-ylamine | C15H17NO | 详情 | 详情 | |
| (XI) | 60278 | N-(2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-yl)acetamide | C17H19NO2 | 详情 | 详情 |