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【结 构 式】 
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【分子编号】50948 【品名】4-chloro-1-[(3,5-dichloro-4-pyridinyl)methyl]-6-methoxyphthalazine; 4-chloro-1-[(3,5-dichloro-4-pyridinyl)methyl]-6-phthalazinyl methyl ether 【CA登记号】 |
【 分 子 式 】C15H10Cl3N3O 【 分 子 量 】354.62212 【元素组成】C 50.8% H 2.84% Cl 29.99% N 11.85% O 4.51% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Friedel-Crafts hydroxymethylation of 3-methoxybenzoic acid (I) using aqueous formaldehyde and HCl gave rise to 6-methoxyisobenzofuran-1-one (II). After radical bromination of (II) with N-bromosuccinimide in the presence of benzoyl peroxide, the resulting 3-bromo derivative (III) was condensed with triphenyl phosphine to afford the phosphonium salt (IV). Wittig condensation of 3,5-dichloropyridine-4-carbaldehyde (V) with the phosphonium bromide (IV) provided the 3-(pyridylmethylene)isobenzofuranone (VI). Reaction of the enol lactone function of (VI) with hydrazine produced the phthalazinone derivative (VII), which was further converted to the 4-chlorophthalazine (VIII) upon treatment with POCl3. The 4-chloro group of (VIII) was finally displaced with the sodium salt of 1,2,4-triazole (IX) to give the title compound.
| 【2】 Norcini, G.; Morazzoni, G.; Leali, G.M.; Napoletano, M.; Grancini, G.; Pellacini, F. (Zambon Group SpA); Phthalazine derivs. phosphodiesterase 4 inhibitors. EP 1097142; US 6329370; WO 0005218 . |
| 【1】 Norcini, G.; Pellacini, F.; Pradella, L.; Marchini, F.; Morazzoni, G.; Ferlenga, P.; Napoletano, M.; Phathalazine PDE4 inhibitors. Part 2: The synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives. Bioorg Med Chem Lett 2001, 11, 1, 33. |
| 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) | 28559 | m-Anisic acid; 3-Methoxybenzoic acid | 586-38-9 | C8H8O3 | 详情 | 详情 |
| (II) | 50943 | 6-methoxyphthalide | C9H8O3 | 详情 | 详情 | |
| (III) | 50944 | 3-bromo-6-methoxy-2-benzofuran-1(3H)-one | C9H7BrO3 | 详情 | 详情 | |
| (IV) | 50945 | (5-methoxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl)(triphenyl)phosphonium bromide | C27H22BrO3P | 详情 | 详情 | |
| (V) | 35536 | 3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde | 136590-83-5 | C6H3Cl2NO | 详情 | 详情 |
| (VI) | 50946 | 3-[(Z)-(3,5-dichloro-4-pyridinyl)methylidene]-6-methoxy-2-benzofuran-1-one | C15H9Cl2NO3 | 详情 | 详情 | |
| (VII) | 50947 | 4-[(3,5-dichloro-4-pyridinyl)methyl]-7-methoxy-1(2H)-phthalazinone | C15H11Cl2N3O2 | 详情 | 详情 | |
| (VIII) | 50948 | 4-chloro-1-[(3,5-dichloro-4-pyridinyl)methyl]-6-methoxyphthalazine; 4-chloro-1-[(3,5-dichloro-4-pyridinyl)methyl]-6-phthalazinyl methyl ether | C15H10Cl3N3O | 详情 | 详情 | |
| (IX) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |