2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol -Drug Synthesis Database

【结构式】

【分子编号】40701

【品名】2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol

【CA登记号】

【分子式】C₁₈H₂₂N₂O₃

【分子量】314.38436

【元素组成】C 68.77% H 7.05% N 8.91% O 15.27%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

Diazotization of p-anisidine (I), followed by coupling of the resulting diazonium salt (II) with 3-tert-butyl-4-hydroxyanisole (III) produced azobenzene (IV). Subsequent protection of the hydroxyl group of (IV) with chloromethyl methyl ether in the presence of NaH afforded the methoxymethyl derivative (V). Aniline (VI) was then obtained by catalytic hydrogenation of (V) over Pd/C. Condensation of aniline (VI) with triphosgene, followed by reaction with 3-picolylamine (VII) gave rise to urea (VIII). The methoxymethyl protecting group of (VIII) was finally removed by treatment with methanolic HCl.

参考文献中间体

合成目标

【1】 Nakao, K.; et al.; Quantitative structure-activity analyses of novel hydroxyphenylurea derivatives as antioxidants. Bioorg Med Chem 1998, 6, 6, 849.
【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 .

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)	10478	p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine	104-94-9	C₇H₉NO	详情	详情
(II)	12149	1-(4-Methoxyphenyl)diazonium chloride		C₇H₇ClN₂O	详情	详情
(III)	40700	2-(tert-butyl)-4-methoxyphenol		C₁₁H₁₆O₂	详情	详情
(IV)	40701	2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol		C₁₈H₂₂N₂O₃	详情	详情
(V)	40702	(Z)-1-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-2-(4-methoxyphenyl)diazene; 3-(tert-butyl)-4-(methoxymethoxy)-5-[(Z)-2-(4-methoxyphenyl)diazenyl]phenyl methyl ether		C₂₀H₂₆N₂O₄	详情	详情
(VI)	40703	3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline		C₁₃H₂₁NO₃	详情	详情
(VII)	18731	3-pyridinylmethanamine; 3-pyridinylmethylamine	3731-52-0	C₆H₈N₂	详情	详情
(VIII)	40704	N-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N'-(3-pyridinylmethyl)urea		C₂₀H₂₇N₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The diazonium salt (VI), prepared by diazotization of p-anisidine (V), was added to 4-methoxy-2-tert-butylphenol (VII) yielding the azo adduct (VIII). Protection of the phenolic hydroxyl group of (VIII) was carried out by alkylation with methoxymethyl chloride and NaH to give methoxymethyl ether (IX). Then, reductive cleavage of the diazo group of (IX) by hydrogenation over Pd/C furnished aniline (X) (1). Subsequent reaction of (X) with triphosgene and triethylamine in cold CH2Cl2 produced isocyanate (XI), which was condensed with amine (IV) to afford urea (XII). After acid deprotection of the methoxymethyl group of (XII), treatment with phosphoric acid in EtOH provided the title triphosphate salt.

参考文献中间体

合成目标

【1】 Kubota, H.; Suzumura, K.; Suzuki, T.; Ohmizu, H.; Kashimura, Y.; Antioxidative property of T-0970, a new ureidophenol derivative. Free Radical Research 2000, 32, 3, 255.
【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	41432	N-(3-pyridinyl)-N-(4-pyridinylmethyl)amine; N-(4-pyridinylmethyl)-3-pyridinamine		C₁₁H₁₁N₃	详情	详情
(V)	10478	p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine	104-94-9	C₇H₉NO	详情	详情
(VI)	41433	4-methoxybenzenediazonium		C₇H₇N₂O	详情	详情
(VII)	40700	2-(tert-butyl)-4-methoxyphenol		C₁₁H₁₆O₂	详情	详情
(VIII)	40701	2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol		C₁₈H₂₂N₂O₃	详情	详情
(IX)	40702	(Z)-1-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-2-(4-methoxyphenyl)diazene; 3-(tert-butyl)-4-(methoxymethoxy)-5-[(Z)-2-(4-methoxyphenyl)diazenyl]phenyl methyl ether		C₂₀H₂₆N₂O₄	详情	详情
(X)	40703	3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline		C₁₃H₂₁NO₃	详情	详情
(XI)	41434	3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl isocyanate; 1-(tert-butyl)-3-isocyanato-5-methoxy-2-(methoxymethoxy)benzene		C₁₄H₁₉NO₄	详情	详情
(XII)	41435	N'-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N-(3-pyridinyl)-N-(4-pyridinylmethyl)urea		C₂₅H₃₀N₄O₄	详情	详情

Extended Information