【结 构 式】 |
【分子编号】14944 【品名】ethyl 4-(3-formyl-4-nitrophenoxy)butanoate 【CA登记号】 |
【 分 子 式 】C13H15NO6 【 分 子 量 】281.26524 【元素组成】C 55.51% H 5.38% N 4.98% O 34.13% |
合成路线1
该中间体在本合成路线中的序号:(III)Alkylation of 5-hydroxy-2-nitrobenzaldehyde (I) with ethyl 4-bromobutyrate (II) in the presence of potassium carbonate at 110 C in DMF provided the aldehyde (III). Coupling of (III) with the phosphonate (IV) using triethylamine as the base afforded the unsaturated hydantoin derivative (V) as a mixture of geometrical isomers. Exhaustive catalytic hydrogenation of (V) over palladium on charcoal in DMF furnished the saturated aniline (VI), which underwent acid-catalyzed cyclization-dehydration in methanol at reflux, followed by oxidation upon addition of a molar equivalent of iodine to give the imidazo[4,5-b]quinoline derivative (VII). Alkaline hydrolysis of (VII) provided acid (VIII), which was coupled with N-cyclohexylmethylpiperazine, using diphenylphosphoryl azide in DMF at room temperature, to furnish BMY 43351 (IX). The dihydrochloride salt of (IX) was prepared by dissolution of the free base in a solution of 10% hydrogen chloride in methanol and subsequent precipitation with diethyl ether.
【1】 Wedding, D.L.; Meanwell, N.A.; Roth, H.R.; Wright, J.J.K.; Smith, E.C.R.; Diethyl 2,4-dioxoimidazolidine-5-phosphonates: Horner-Wadsworth-Emmons reagents for the mild and efficient preparations of C-5 unsaturated hydantoin derivatives. J Org Chem 1991, 56, 6897-904. |
【2】 Russell, J.W.; Seiler, S.M.; Meanwell, N.A.; Fleming, J.S.; BMY 43351. Drugs Fut 1992, 17, 1, 15. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
63929 | 1-(cyclohexylmethyl)piperazine | C11H22N2 | 详情 | 详情 | ||
(I) | 14942 | 5-hydroxy-2-nitrobenzaldehyde | 42454-06-8 | C7H5NO4 | 详情 | 详情 |
(II) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
(III) | 14944 | ethyl 4-(3-formyl-4-nitrophenoxy)butanoate | C13H15NO6 | 详情 | 详情 | |
(IV) | 14945 | Diethyl 5-hydantoylphosphonate; diethyl 2,5-dioxo-4-imidazolidinylphosphonate | 95378-36-2 | C7H13N2O5P | 详情 | 详情 |
(V) | 14946 | ethyl 4-[3-[(2,5-dioxotetrahydro-4H-imidazol-4-ylidene)methyl]-4-nitrophenoxy]butanoate | C16H17N3O7 | 详情 | 详情 | |
(VI) | 14947 | ethyl 4-[4-amino-3-[(2,5-dioxo-4-imidazolidinyl)methyl]phenoxy]butanoate | C16H21N3O5 | 详情 | 详情 | |
(VII) | 14948 | methyl 4-[(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]quinolin-7-yl)oxy]butanoate | C15H15N3O4 | 详情 | 详情 | |
(VIII) | 14949 | 4-[(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]quinolin-7-yl)oxy]butyric acid | C14H13N3O4 | 详情 | 详情 | |
(IX) | 14950 | 7-[4-[4-(cyclohexylmethyl)piperazino]-4-oxobutoxy]-1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one | C25H33N5O3 | 详情 | 详情 |