3-phenyl-7-propyl-1,2-benzisoxazol-6-ol -Drug Synthesis Database

【结构式】

【分子编号】63552

【品名】3-phenyl-7-propyl-1,2-benzisoxazol-6-ol

【CA登记号】

【分子式】C₁₆H₁₅NO₂

【分子量】253.30064

【元素组成】C 75.87% H 5.97% N 5.53% O 12.63%

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：(V)

Claisen rearrangement of allyl ether (I) in refluxing o-dichlorobenzene affords (II). The allyl group of (II) is subsequently hydrogenated over Pd/C to provide the propyl derivative (III). Benzophenone (III) is converted into the corresponding oxime (IV) by means of hydroxylamine hydrochloride and NaOAc. Acetylation of oxime (IV), followed by refluxing in pyridine gives rise to the benzisoxazole (V). The phenolic hydroxyl group of (V) is then alkylated by 1,4-dibromobutane (VI) producing the bromobutyl ether (VII). 3-Hydroxyphenylacetic acid (VIII) is esterified with MeOH/H2SO4 to give the methyl ester (IX). This is then condensed with bromide (VII) in the presence of K2CO3 to furnish diether (X). Finally, saponification of the methyl ester group of (X) employing LiOH yields the target carboxylic acid (1,2)

参考文献中间体

合成目标

【1】 Adams, A.D.; Yuen, W.; Hu, Z.; Santini, C.; Jones, A.B.; MacNaul, K.L.; Berger, J.P.; Doebber, T.W.; Moller, D.E.; Amphipathic 3-phenyl-7-propylbenzisoxazoles; human PPAR gamma, delta and alpha agonists. Bioorg Med Chem Lett 2003, 13, 5, 931.
【2】 Adams, A.D.; Berger, J.P.; Berger, G.D.; Fitch, K.J.; Graham, D.W.; Jones, A.B.; Von Langen, D.; Leibowitz, M.D.; Moller, D.E.; Patchett, A.A.; Santini, C.; Sahoo, S.P.; Tolman, R.L.; Toupence, R.B.; Walsh, T.F. (Merck & Co., Inc.); Heterocyclic derivs. as antidiabetic and antiobesity agents. EP 0882029; JP 2002503203; US 6090836; WO 9728137 .

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)	63548	[4-(allyloxy)-2-hydroxyphenyl](phenyl)methanone		C₁₆H₁₄O₃	详情	详情
(II)	63549	(3-allyl-2,4-dihydroxyphenyl)(phenyl)methanone		C₁₆H₁₄O₃	详情	详情
(III)	63550	(2,4-dihydroxy-3-propylphenyl)(phenyl)methanone		C₁₆H₁₆O₃	详情	详情
(IV)	63551	(2,4-dihydroxy-3-propylphenyl)(phenyl)methanone oxime		C₁₆H₁₇NO₃	详情	详情
(V)	63552	3-phenyl-7-propyl-1,2-benzisoxazol-6-ol		C₁₆H₁₅NO₂	详情	详情
(VI)	11883	1,4-Dibromobutane; 1,4-Butylene bromide	110-52-1	C₄H₈Br₂	详情	详情
(VII)	63553	6-(4-bromobutoxy)-3-phenyl-7-propyl-1,2-benzisoxazole; 4-bromobutyl 3-phenyl-7-propyl-1,2-benzisoxazol-6-yl ether		C₂₀H₂₂BrNO₂	详情	详情
(VIII)	58561	2-(3-hydroxyphenyl)acetic acid		C₈H₈O₃	详情	详情
(IX)	58567	methyl 2-(3-hydroxyphenyl)acetate		C₉H₁₀O₃	详情	详情
(X)	63554	methyl 2-(3-{4-[(3-phenyl-7-propyl-1,2-benzisoxazol-6-yl)oxy]butoxy}phenyl)acetate		C₂₉H₃₁NO₅	详情	详情

Extended Information