3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid -Drug Synthesis Database

【结构式】

【分子编号】63734

【品名】3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid

【CA登记号】

【分子式】C₁₉H₁₅F₂N₃O₅

【分子量】403.3421264

【元素组成】C 56.58% H 3.75% F 9.42% N 10.42% O 19.83%

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：(XI)

Deprotection of N-Boc-D-3,4-difluorophenylalanine (V) by means of HCl in dioxane yields aminoacid (VI). Subsequent diazotization of (VI) with NaNO2/H2SO4 leads to hydroxyacid (VII). After esterification of (VII) with methanolic HCl, the hydroxyester (VIII) is converted into triflate (IX) upon treatment with trifluoromethanesulfonic anhydride and 2,6-lutidine. Condensation of hydroxypyridine (IV) with triflate (IX) in the presence of NaH gives rise to the N-alkylated pyridone (X). The methyl ester group of (X) is then hydrolyzed to the corresponding carboxylic acid (XI) by means of either NaOH or LiI in pyridine. (1,2)

参考文献中间体

合成目标

【1】 Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors: 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics. J Med Chem 2002, 45, 8, 1607.
【2】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; Johnson, T.O. Jr. (Agouron Pharmaceuticals, Inc.); Antipicornaviral cpds. and compsns., their pharmaceutical uses, and material for their synthesis. JP 2003515591; US 2001047006; US 6514997; WO 0140189 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	63727	N-(2-hydroxy-3-pyridinyl)-5-methyl-3-isoxazolecarboxamide	C₁₀H₉N₃O₃	详情	详情
(V)	63728	N-{[(1,1-dimethylethyl)oxy]carbonyl}-3,4-difluorophenylalanine	C₁₄H₁₇F₂NO₄	详情	详情
(VI)	63729	3,4-difluorophenylalanine	C₉H₉F₂NO₂	详情	详情
(VII)	63730	3-(3,4-difluorophenyl)-2-hydroxypropanoic acid	C₉H₈F₂O₃	详情	详情
(VIII)	63731	methyl 3-(3,4-difluorophenyl)-2-hydroxypropanoate	C₁₀H₁₀F₂O₃	详情	详情
(IX)	63732	methyl 3-(3,4-difluorophenyl)-2-{[(trifluoromethyl)sulfonyl]oxy}propanoate	C₁₁H₉F₅O₅S	详情	详情
(X)	63733	methyl 3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoate	C₂₀H₁₇F₂N₃O₅	详情	详情
(XI)	63734	3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid	C₁₉H₁₅F₂N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Treatment of the Boc-protected aminoalcohol (XII) with trifluoroacetic acid furnishes (XIII). This is then coupled with acid (XI) in the presence of HATU to afford the amide alcohol (XIV). Oxidation of (XIV) with the Dess-Martin periodinane (DMP) reagent gives rise to aldehyde (XV). Finally, Wittig condensation of aldehyde (XV) with isopropoxycarbonylmethylene triphenylphosphorane provides the target unsaturated ester. (1,2)

参考文献中间体

合成目标

【1】 Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors: 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics. J Med Chem 2002, 45, 8, 1607.
【2】 Dragovich, P.S.; Prins, T.J.; Zhou, R.; Johnson, T.O. Jr. (Agouron Pharmaceuticals, Inc.); Antipicornaviral cpds. and compsns., their pharmaceutical uses, and material for their synthesis. JP 2003515591; US 2001047006; US 6514997; WO 0140189 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	63734	3-(3,4-difluorophenyl)-2-[3-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-2-oxo-1(2H)-pyridinyl]propanoic acid	C₁₉H₁₅F₂N₃O₅	详情	详情
(XII)	55039	tert-butyl (1S)-2-hydroxy-1-{[(3S)-2-oxopyrrolidinyl]methyl}ethylcarbamate	C₁₂H₂₂N₂O₄	详情	详情
(XIII)	63735	3-(2-amino-3-hydroxypropyl)-2-pyrrolidinone	C₇H₁₄N₂O₂	详情	详情
(XIV)	63736	N-{1-[1-[(3,4-difluorophenyl)methyl]-2-({2-hydroxy-1-[(2-oxo-3-pyrrolidinyl)methyl]ethyl}amino)-2-oxoethyl]-2-oxo-1,2-dihydro-3-pyridinyl}-5-methyl-3-isoxazolecarboxamide	C₂₆H₂₇F₂N₅O₆	详情	详情
(XV)	63737	N-[1-(1-[(3,4-difluorophenyl)methyl]-2-{[1-formyl-2-(2-oxo-3-pyrrolidinyl)ethyl]amino}-2-oxoethyl)-2-oxo-1,2-dihydro-3-pyridinyl]-5-methyl-3-isoxazolecarboxamide	C₂₆H₂₅F₂N₅O₆	详情	详情

Extended Information