methyl 3-[3-[(1S)-1-amino-3-methylbutyl]-5-isoxazolyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】51635

【品名】methyl 3-[3-[(1S)-1-amino-3-methylbutyl]-5-isoxazolyl]propanoate

【CA登记号】

【分子式】C₁₂H₂₀N₂O₃

【分子量】240.30248

【元素组成】C 59.98% H 8.39% N 11.66% O 19.97%

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)

The isoxazolepropionate intermediate (IV) has been obtained as follows: The cyclization of N-(tert-butoxycarbonyl)-L-leucinal oxime (I) with 4-pentynoic acid methyl ester (II) by means of NaOCl and TEA in dichloromethane gives the protected isoxazole derivative (III), which is then treated with Cl in dioxane to afford the desired isoxazole intermediate (IV).

参考文献中间体

合成目标

【1】 Duplantier, A.J.; et al.; Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha4beta1 integrin antagonists. Bioorg Med Chem Lett 2001, 11, 19, 2593.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	51632	tert-butyl (1S)-1-[(hydroxyimino)methyl]-3-methylbutylcarbamate	C₁₁H₂₂N₂O₃	详情	详情
(II)	51633	methyl 4-pentynoate	C₆H₈O₂	详情	详情
(III)	51634	methyl 3-(3-[(1S)-1-[(tert-butoxycarbonyl)amino]-3-methylbutyl]-5-isoxazolyl)propanoate	C₁₇H₂₈N₂O₅	详情	详情
(IV)	51635	methyl 3-[3-[(1S)-1-amino-3-methylbutyl]-5-isoxazolyl]propanoate	C₁₂H₂₀N₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of 5-chloro-2-nitroanisole (V) with diethyl malonate (VI) by means of NaH in hot DMF gives 2-(3-methoxy-4-nitrophenyl)malonic acid diethyl ester (VII), which is reduced with H2 over Pd/C in ethyl acetate, yielding the corresponding amino derivative (VIII). The condensation of (VIII) with 2-methylphenyl isocyanate (IX) by means of TEA in dichloromethane affords the expected urea (X), which is submitted to a decarboxylative hydrolysis with NaOH in refluxing tert-butanol to provide the phenylacetic acid (XI). The condensation of acetic acid (XI) with the amino group of the isoxazole intermediate (IV) by means of HOBt, DIEA and EDC in DMF gives the amide (XII), which is treated with NaOH in tert-butanol to afford the target propionic acid.

参考文献中间体

合成目标

【1】 Duplantier, A.J.; et al.; Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha4beta1 integrin antagonists. Bioorg Med Chem Lett 2001, 11, 19, 2593.

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)	51635	methyl 3-[3-[(1S)-1-amino-3-methylbutyl]-5-isoxazolyl]propanoate		C₁₂H₂₀N₂O₃	详情	详情
(V)	51636	4-Chloro-2-methoxy-1-nitrobenzene; 4-Chloro-2-methoxynitrobenzene; 5-Chloro-2-nitroanisole	6627-53-8	C₇H₆ClNO₃	详情	详情
(VI)	16829	Diethyl malonate	105-53-3	C₇H₁₂O₄	详情	详情
(VII)	51637	diethyl 2-(3-methoxy-4-nitrophenyl)malonate		C₁₄H₁₇NO₇	详情	详情
(VIII)	51638	diethyl 2-(4-amino-3-methoxyphenyl)malonate		C₁₄H₁₉NO₅	详情	详情
(IX)	27106	1-isocyanato-2-methylbenzene	614-68-6	C₈H₇NO	详情	详情
(X)	51639	diethyl 2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]malonate		C₂₂H₂₆N₂O₆	详情	详情
(XI)	39718	2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid		C₁₇H₁₈N₂O₄	详情	详情
(XII)	51640	methyl 3-(3-[(1S)-1-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]-3-methylbutyl]-5-isoxazolyl)propanoate		C₂₉H₃₆N₄O₆	详情	详情

Extended Information