methyl 2-(3-aminophenyl)acetate -Drug Synthesis Database

【结构式】

【分子编号】41111

【品名】methyl 2-(3-aminophenyl)acetate

【CA登记号】

【分子式】C₉H₁₁NO₂

【分子量】165.19188

【元素组成】C 65.44% H 6.71% N 8.48% O 19.37%

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：(X)

Coupling of 2-benzyloxyaniline (I) with N-Boc-glycine (II) by means of EDC aforded amide (III). Subsequent N-alkylation of (III) with N-methyl-N-phenyl-2-bromoacetamide (IV) in the presence of NaH provided diamide (V). Hydrogenolysis of the benzyl ether of (V) over Pd/C gave phenol derivative (VI) (1). Phenol (VI) was then alkylated with bromoamide (IV) to furnish ether (VII). After cleavage of the Boc group of (VII) with trifluoroacetic acid, the resulting amine (VIII) was reacted with carbonyldiimidazole to produce imidazolide (IX), which was subsequently coupled with aniline (X) yielding urea (XI). Finally, basic hydrolysis of the methyl ester group of (XI) gave the title carboxylic acid.

参考文献中间体

合成目标

【1】 Yokomizo, A.; Takeda, Y.; Kawagoe, K.; et al.; Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. II. Chem Pharm Bull 1998, 46, 6, 951.
【2】 Yokohama, S.; Kawagoe, K.; Takeda, Y.; Yokomizo, Y.; Yokomizo, A. (Daiichi Pharmaceutical Co., Ltd.); Aminophenol derivs.. EP 0985660; US 5919824; WO 9628416 .

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)	18065	2-(benzyloxy)aniline; 2-(benzyloxy)phenylamine		C₁₃H₁₃NO	详情	详情
(II)	18066	N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid	4530-20-5	C₇H₁₃NO₄	详情	详情
(III)	18067	tert-butyl 2-[2-(benzyloxy)anilino]-2-oxoethylcarbamate		C₂₀H₂₄N₂O₄	详情	详情
(IV)	18068	2-bromo-N-methyl-N-phenylacetamide		C₉H₁₀BrNO	详情	详情
(V)	18069	tert-butyl 2-[2-(benzyloxy)[2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate		C₂₉H₃₃N₃O₅	详情	详情
(VI)	41107	tert-butyl 2-[2-hydroxy[2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate		C₂₂H₂₇N₃O₅	详情	详情
(VII)	41108	tert-butyl 2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethylcarbamate		C₃₁H₃₆N₄O₆	详情	详情
(VIII)	41109	2-amino-N-[2-[2-(methylanilino)-2-oxoethoxy]phenyl]-N-[2-(methylanilino)-2-oxoethyl]acetamide		C₂₆H₂₈N₄O₄	详情	详情
(IX)	41110	N-(2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethyl)-1H-imidazole-1-carboxamide		C₃₀H₃₀N₆O₅	详情	详情
(X)	41111	methyl 2-(3-aminophenyl)acetate		C₉H₁₁NO₂	详情	详情
(XI)	41112	methyl 2-[3-([[(2-[2-[2-(methylanilino)-2-oxoethoxy][2-(methylanilino)-2-oxoethyl]anilino]-2-oxoethyl)amino]carbonyl]amino)phenyl]acetate		C₃₆H₃₇N₅O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarbonyl chloride (I) with methyl 3-aminophenylacetate (II) leads to amide (III). Intramolecular cyclization of (III) and simultaneous hydrolysis in the presence of NaOH in MeOH/DMF provide the isoxazoloquinoline derivative (IV). After activation of acid (IV) as the corresponding acid chloride (V), coupling with 3,4,5-trimethoxyaniline (VI) furnishes the title compound

参考文献中间体

合成目标

【1】 Norman, B.H.; et al.; Tricyclic isoxazoles are novel inhibitors of the multidrug resistance protein (MRP1). Bioorg Med Chem Lett 2002, 12, 6, 883.
【2】 Kroin, J.S.; Norman, B.H.; Gruber, J.M. (Eli Lilly and Company); Methods for inhibiting MRP1. EP 1067928; JP 2002510625; US 6369070; WO 9951228 .

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)	59641	3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarbonyl chloride		C₁₁H₆Cl₂FNO₂	详情	详情
(II)	41111	methyl 2-(3-aminophenyl)acetate		C₉H₁₁NO₂	详情	详情
(III)	62525	methyl 2-[3-({[3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl]carbonyl}amino)phenyl]acetate		C₂₀H₁₆ClFN₂O₄	详情	详情
(IV)	62526	2-{3-[9-chloro-3-methyl-4-oxoisoxazolo[4,3-c]quinolin-5(4H)-yl]phenyl}acetic acid		C₁₉H₁₃ClN₂O₄	详情	详情
(V)	62527	2-{3-[9-chloro-3-methyl-4-oxoisoxazolo[4,3-c]quinolin-5(4H)-yl]phenyl}acetyl chloride		C₁₉H₁₂Cl₂N₂O₃	详情	详情
(VI)	31545	3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine	24313-88-0	C₉H₁₃NO₃	详情	详情

Extended Information