tert-butyl 5-amino-2,4-difluorophenylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】38179

【品名】tert-butyl 5-amino-2,4-difluorophenylcarbamate

【CA登记号】

【分子式】C₁₁H₁₄F₂N₂O₂

【分子量】244.2412464

【元素组成】C 54.09% H 5.78% F 15.56% N 11.47% O 13.1%

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：(VII)

Methyl 4-amino-2,5-difluoro-3-methylbenzoate (I) was oxidized to the corresponding nitro derivative (II) with sodium perborate in TFA-AcOH. Acid hydrolysis of the methyl ester afforded carboxylic acid (III), which was converted into acid chloride (IV) employing oxalyl chloride and a catalytic amount of DMF. Condensation of (IV) with the magnesium salt of diethyl malonate, followed by acid-catalyzed decarbethoxylation gave rise to keto ester (V). Subsequent condensation of (V) with triethyl orthoformate in the presence of acetic anhydride yielded the ethoxymethylene derivative (VI). Reaction of (VI) with aniline (VII) followed by cyclization of the intermediate enamine in the presence of K2CO3 afforded quinolone (VIII). The nitro group of (VIII) was then reduced to aniline (IX) by means of iron and AcOH. Finally, acid deprotection of the Boc group of (IX) gave the title compound.

参考文献中间体

合成目标

【1】 Sakae, N.; Yazaki, A.; Kuramoto, Y.; Yoshida, J.; Niino, Y.; Oshita, Y.; Hirao, Y.; Hayashi, N.; Amano, H. (Wakunaga Pharmaceutical Co., Ltd.); Novel pyridonecarboxylic acid derivs. or salts thereof and drugs containing the same as the active ingredient. EP 0945435; WO 9823592 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	28858	diethyl ethoxymagnesiummalonate	C₉H₁₆MgO₅	详情	详情
(I)	38173	methyl 4-amino-2,5-difluoro-3-methylbenzoate	C₉H₉F₂NO₂	详情	详情
(II)	38174	methyl 2,5-difluoro-3-methyl-4-nitrobenzoate	C₉H₇F₂NO₄	详情	详情
(III)	38175	2,5-difluoro-3-methyl-4-nitrobenzoic acid	C₈H₅F₂NO₄	详情	详情
(IV)	38176	2,5-difluoro-3-methyl-4-nitrobenzoyl chloride	C₈H₄ClF₂NO₃	详情	详情
(V)	38177	ethyl 3-(2,5-difluoro-3-methyl-4-nitrophenyl)-3-oxopropanoate	C₁₂H₁₁F₂NO₅	详情	详情
(VI)	38178	ethyl (Z)-2-(2,5-difluoro-3-methyl-4-nitrobenzoyl)-3-ethoxy-2-propenoate	C₁₅H₁₅F₂NO₆	详情	详情
(VII)	38179	tert-butyl 5-amino-2,4-difluorophenylcarbamate	C₁₁H₁₄F₂N₂O₂	详情	详情
(VIII)	38180	ethyl 1-[5-[(tert-butoxycarbonyl)amino]-2,4-difluorophenyl]-6-fluoro-8-methyl-7-nitro-4-oxo-1,4-dihydro-3-quinolinecarboxylate	C₂₄H₂₂F₃N₃O₇	详情	详情
(IX)	38181	ethyl 7-amino-1-[5-[(tert-butoxycarbonyl)amino]-2,4-difluorophenyl]-6-fluoro-8-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxylate	C₂₄H₂₄F₃N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Treatment of benzoylacetate derivative (I) with triethyl orthoformate and Ac2O yields derivative (II), which is then subjected to cyclization with N-tert-buxoxycarbonyl-2,4-difluoro-m-phenylenediamine (III) in EtOH, followed by treatment with K2CO3 in DMF, to afford dihydroquinoline ethyl carboxylate derivative (IV). Simultaneous hydrolysis and Boc removal of (IV) with HCl gives carboxylic acid (V), which is then treated with an aqueous solution of methylamine in the presence of pyridine to provide derivative (VI). Finally, the ethanolamine salt of the compound is formed by treatment of (VI) with ethanolamine and pyridine.

参考文献中间体

合成目标

【1】 Sakae, N.; Yazaki, A.; Kuramoto, Y.; Yoshida, J.; Niino, Y.; Oshita, Y.; Hirao, Y.; Hayashi, N.; Amano, H. (Wakunaga Pharmaceutical Co., Ltd.); Novel pyridonecarboxylic acid derivs. or salts thereof and drugs containing the same as the active ingredient. EP 0945435; WO 9823592 .

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)	45986	ethyl 3-oxo-3-(2,4,5-trifluoro-3-methylphenyl)propanoate		C₁₂H₁₁F₃O₃	详情	详情
(II)	45987	ethyl (Z)-3-ethoxy-2-(2,4,5-trifluoro-3-methylbenzoyl)-2-propenoate		C₁₅H₁₅F₃O₄	详情	详情
(III)	38179	tert-butyl 5-amino-2,4-difluorophenylcarbamate		C₁₁H₁₄F₂N₂O₂	详情	详情
(IV)	45988	ethyl 1-[5-[(tert-butoxycarbonyl)amino]-2,4-difluorophenyl]-6,7-difluoro-8-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₂₄H₂₂F₄N₂O₅	详情	详情
(V)	45989	1-(5-amino-2,4-difluorophenyl)-6,7-difluoro-8-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₇H₁₀F₄N₂O₃	详情	详情
(VI)	45990	1-(5-amino-2,4-difluorophenyl)-6-fluoro-8-methyl-7-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₈H₁₄F₃N₃O₃	详情	详情
(VII)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情

Extended Information