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【结 构 式】

【分子编号】50943

【品名】6-methoxyphthalide

【CA登记号】

【 分 子 式 】C9H8O3

【 分 子 量 】164.16072

【元素组成】C 65.85% H 4.91% O 29.24%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

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
Extended Information