5-(4-methylphenyl)isoxazole -Drug Synthesis Database

【结构式】

【分子编号】26770

【品名】5-(4-methylphenyl)isoxazole

【CA登记号】

【分子式】C₁₀H₉NO

【分子量】159.1876

【元素组成】C 75.45% H 5.7% N 8.8% O 10.05%

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：(III)

4'-Methylacetophenone (I) was condensed with boiling dimethylformamide dimethylacetal, and the resulting enaminoketone (II) was cyclized to the isoxazole (III) with hydroxylamine O-sulfonic acid in MeOH. Benzylic bromination of (III) with N-bromosuccinimide in the presence of benzoyl peroxide gave bromomethyl compound (IV). Subsequent alkylation of diphenylmethylene glycine ethyl ester (V) with (IV) under phase-transfer conditions, followed by acid deprotection furnished isoxazolylphenylalanine ethyl ester (VII). This compound was condensed with 3,5-dimethyl benzoic acid (VIII) using EDC and HOBt to give amide (IX). Further N-methylation of (IX) with MeI and NaH yielded (X), which was hydrolyzed with LiOH to the carboxylic acid (XI).

参考文献中间体

合成目标

【1】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Frueh, T.; Pitterna, T.; Iwasaki, G.; Oda, K.; Yamamura, T.; Hayakawa, K.; Discovery of IRL 3461: A novel and potent endothelin antagonist with balanced ETA/ETB affinity. Bioorg Med Chem Lett 1998, 8, 16, 2241.
【2】 Fruh, T.; Pitterna, T.; Murata, T.; Svensson, L.D.; Yuumoto, Y.; Sakaki, J. (Novartis Japan KK); Antagonists of endothelin receptors. EP 0753004; JP 1997510720; US 5703106; WO 9526360 .

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)	17145	1-(4-methylphenyl)-1-ethanone; p-methylacetophenone; 4-methylacetophenone; 4-methylphenylethanone	122-00-9	C₉H₁₀O	详情	详情
(II)	26769	(E)-3-(dimethylamino)-1-(4-methylphenyl)-2-propen-1-one		C₁₂H₁₅NO	详情	详情
(III)	26770	5-(4-methylphenyl)isoxazole		C₁₀H₉NO	详情	详情
(IV)	26771	5-[4-(bromomethyl)phenyl]isoxazole		C₁₀H₈BrNO	详情	详情
(V)	26772	ethyl 2-((diphenylmethylene)amino)acetate;N-(Diphenylmethylene)glycine ethyl ester;Ethyl N-(diphenylmethylene)glycinate;ethyl 2-[(dibenzylene)amino]acetate	69555-14-2	C₁₇H₁₇NO₂	详情	详情
(VI)	26773	ethyl 2-[(dibenzylene)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₇H₂₄N₂O₃	详情	详情
(VII)	26774	ethyl 2-amino-3-[4-(5-isoxazolyl)phenyl]propanoate		C₁₄H₁₆N₂O₃	详情	详情
(VIII)	26775	3,5-dimethylbenzoic acid	499-06-9	C₉H₁₀O₂	详情	详情
(IX)	26776	ethyl 2-[(3,5-dimethylbenzoyl)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₃H₂₄N₂O₄	详情	详情
(X)	26777	ethyl 2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₄H₂₆N₂O₄	详情	详情
(XI)	26778	N-(3,5-dimethylbenzoyl)-4-(5-isoxazolyl)-N-methylphenylalanine		C₂₂H₂₂N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Hayakawa, K.; Stereoselective synthesis of a novel and bifunctional endothelin antagonist, IRL 3630. Bioorg Med Chem Lett 1998, 8, 16, 2247.
【2】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Okada, T. (Novartis Japan KK); Antagonists of endothelin receptors. JP 1999512702; WO 9711960 .

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)	17145	1-(4-methylphenyl)-1-ethanone; p-methylacetophenone; 4-methylacetophenone; 4-methylphenylethanone	122-00-9	C₉H₁₀O	详情	详情
(II)	26769	(E)-3-(dimethylamino)-1-(4-methylphenyl)-2-propen-1-one		C₁₂H₁₅NO	详情	详情
(III)	26770	5-(4-methylphenyl)isoxazole		C₁₀H₉NO	详情	详情
(IV)	26771	5-[4-(bromomethyl)phenyl]isoxazole		C₁₀H₈BrNO	详情	详情
(V)	26772	ethyl 2-((diphenylmethylene)amino)acetate;N-(Diphenylmethylene)glycine ethyl ester;Ethyl N-(diphenylmethylene)glycinate;ethyl 2-[(dibenzylene)amino]acetate	69555-14-2	C₁₇H₁₇NO₂	详情	详情
(VI)	26773	ethyl 2-[(dibenzylene)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₇H₂₄N₂O₃	详情	详情
(VII)	26774	ethyl 2-amino-3-[4-(5-isoxazolyl)phenyl]propanoate		C₁₄H₁₆N₂O₃	详情	详情
(VIII)	26775	3,5-dimethylbenzoic acid	499-06-9	C₉H₁₀O₂	详情	详情
(IX)	26776	ethyl 2-[(3,5-dimethylbenzoyl)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₃H₂₄N₂O₄	详情	详情
(X)	26777	ethyl 2-[(3,5-dimethylbenzoyl)(methyl)amino]-3-[4-(5-isoxazolyl)phenyl]propanoate		C₂₄H₂₆N₂O₄	详情	详情
(XI)	26778	N-(3,5-dimethylbenzoyl)-4-(5-isoxazolyl)-N-methylphenylalanine		C₂₂H₂₂N₂O₄	详情	详情

Extended Information