(E)-3-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-propenoic acid -Drug Synthesis Database

【结构式】

【分子编号】43375

【品名】(E)-3-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-propenoic acid

【CA登记号】22014-01-3

【分子式】C₁₇H₂₄O₃

【分子量】276.37576

【元素组成】C 73.88% H 8.75% O 17.37%

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：(I)

Catalytic hydrogenation of 3,5-di-tert-butyl-4-hydroxycinnamic acid (I) afforded the saturated carboxylic acid (II), which was converted into amide (IV) via the corresponding acid chloride (III). Reduction of the amide function of (IV) by means of LiAlH4 furnished the primary amine (V). This was condensed with O-benzyl maltol (VI) to produce the pyridone (VII). After hydrogenolysis of the benzyl protecting group of (VII), the title compound was isolated as the corresponding mesylate salt.

参考文献中间体

合成目标

【1】 Malcolm, C.S.; Bebbington, D.; Monck, N.J.T.; Palmer, A.M.; Gaur, S.; Benwell, K.; Porter, R.H.P.; Harvey, V.; 3,5-Disubstituted-4-hydroxyphenyls linked to 3-hydroxy-2-methyl-4(1H)-pyridinone: Potent inhibitors of lipid peroxidation and cell toxicity. J Med Chem 2000, 43, 15, 2779.
【2】 Malcolm, C.; Porter, R.; Bebbington, D.; Palmer, A.; Gaur, S.; Monck, N. (Vernalis Research Ltd.); Ortho-hydroxypyridinone derivs. as iron chelating and antioxidant agents. EP 1027335; WO 9923075 .

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)	43375	(E)-3-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-propenoic acid	22014-01-3	C₁₇H₂₄O₃	详情	详情
(II)	43376	3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propionic acid	20170-32-5	C₁₇H₂₆O₃	详情	详情
(III)	43777	5,5,8,8-tetramethyl-N-(2-nitrophenyl)-5,6,7,8-tetrahydro-2-naphthalenamine; N-(2-nitrophenyl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amine		C₂₀H₂₄N₂O₂	详情	详情
(IV)	43378	3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propanamide		C₁₇H₂₇NO₂	详情	详情
(V)	43379	4-(3-aminopropyl)-2,6-di(tert-butyl)phenol		C₁₇H₂₉NO	详情	详情
(VI)	12074	3-(Benzyloxy)-2-methyl-4H-pyran-4-one；3-(benzyloxy)-2-methylpyran-4-one	61049-69-2	C₁₃H₁₂O₃	详情	详情
(VII)	43380	3-(benzyloxy)-1-[3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propyl]-2-methyl-4(1H)-pyridinone		C₃₀H₃₉NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Nitrosation of pyrimidinedione (I) with NaNO2/HCl affords (II), which is further reduced to the diaminopyrimidine (III) by catalytic hydrogenation over Pd/C. Subsequent coupling of (III) with 2,6-di-tert-butyl-4-hydroxycinnamic acid (IV) employing DPP-Cl furnishes the title amide

参考文献中间体

合成目标

【1】 Isobe, Y.; Tobe, M.; Inoue, Y.; Goto, Y.; Obara, F.; Isobe, M.; Hayashi, H.; Inhibitory activities of novel pyrimidine derivatives on the contact hypersensitivity reaction. Chem Pharm Bull 2003, 51, 3, 309.

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)	44183	6-amino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₁N₃O₂	详情	详情
(II)	63475	6-amino-3-methyl-5-nitroso-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₀N₄O₃	详情	详情
(III)	44185	5,6-diamino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₂N₄O₂	详情	详情
(IV)	43375	(E)-3-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-propenoic acid	22014-01-3	C₁₇H₂₄O₃	详情	详情

Extended Information