2-amino-3-nitrophenol -Drug Synthesis Database

【结构式】

【分子编号】41985

【品名】2-amino-3-nitrophenol

【CA登记号】603-85-0

【分子式】C₆H₆N₂O₃

【分子量】154.12532

【元素组成】C 46.76% H 3.92% N 18.18% O 31.14%

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：(I)

Alkylation of 2-amino-3-nitrophenol (I) with 1,2-dichloroethane in 2-butanone afforded the chloroethyl ether (II), which was further condensed with benzylamine (III) to give amine (IV) (1,2). Acylation of (IV) with trifluoroacetic anhydride provided trifluoroacetamide (V). The nitro group of (V) was then reduced by transfer hydrogenation using hydrazine and Pd/C. Cyclization of the resulting phenylenediamine (VI) in refluxing TFA gave rise to benzimidazole (VII). The trifluoroacetamido group of (VII) was finally removed by treatment with K2CO3 in boiling MeOH (1). In a more direct procedure, nitroaniline (IV) was reduced to diamine (VIII) and then cyclized to the title benzimidazole by treatment with TFA.

参考文献中间体

合成目标

【1】 Brennan, J.A.; Coupet, J.; Mazandarani, H.; Andree, T.H.; Nelson, J.A.; Marquis, K.; Shi, X.; Shah, U.S.; Mewshaw, R.E.; New generation dopaminergic agents 7. heterocyclic bioisosteres that exploit the 3-OH-phenoxyethylamine D2 template. Bioorg Med Chem Lett 1999, 9, 17, 2593.
【2】 Nelson, J.A.; Mewshaw, R.E. (American Home Products Corp.); 4-Aminoalkoxy-1H-benzimidazole derivs., their preparation and their use as dopamine autoreceptor (D2) agonists. EP 0973749; WO 9835945 .

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)	41985	2-amino-3-nitrophenol	603-85-0	C₆H₆N₂O₃	详情	详情
(II)	41986	2-(2-chloroethoxy)-6-nitrophenylamine; 2-(2-chloroethoxy)-6-nitroaniline		C₈H₉ClN₂O₃	详情	详情
(III)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(IV)	41987	2-[2-(benzylamino)ethoxy]-6-nitroaniline; N-[2-(2-amino-3-nitrophenoxy)ethyl]-N-benzylamine		C₁₅H₁₇N₃O₃	详情	详情
(V)	41988	N-[2-(2-amino-3-nitrophenoxy)ethyl]-N-benzyl-2,2,2-trifluoroacetamide		C₁₇H₁₆F₃N₃O₄	详情	详情
(VI)	41989	N-benzyl-N-[2-(2,3-diaminophenoxy)ethyl]-2,2,2-trifluoroacetamide		C₁₇H₁₈F₃N₃O₂	详情	详情
(VII)	41990	N-benzyl-2,2,2-trifluoro-N-(2-[[2-(trifluoromethyl)-1H-benzimidazol-4-yl]oxy]ethyl)acetamide		C₁₉H₁₅F₆N₃O₂	详情	详情
(VIII)	41991	2-amino-3-[2-(benzylamino)ethoxy]phenylamine; 3-[2-(benzylamino)ethoxy]-1,2-benzenediamine		C₁₅H₁₉N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

Sandmeyer reaction of 2-amino-3-nitrophenol (XXVI) using NaNO2 and HBr in the presence of CuBr in H2O/dioxane gives 2-bromo-3-nitrophenol (XXVII), which by O-alkylation with MeI in the presence of Cs2CO3 in DMF affords the methyl ether (XXVIII). Subsequent reduction of the nitro derivative (XXVIII) with Fe powder in refluxing AcOH/EtOH provides 2-bromo-3-methoxyaniline (XXIX) . Addition of aniline (XXIX) to dimethyl acetylene dicarboxylate (XXX) in refluxing MeOH produces the amino diester (XXXI), which by cyclization at 240 °C in diphenyl ether affords the quinoline (X) .

参考文献中间体

合成目标

【1】 Llinas-Brunet, M., Bailey, M.D., Goudreau, N. et al. Discovery of a potent and selective noncovalent linear inhibitor of the hepatitis C virus NS3 protease (BI 201335). J Med Chem 2010, 53(17): 6466-76.
【2】 Llinas-Brunet, M., Bailey, M., Bhardwaj, P. et al. (Boehringer Ingelheim International GmbH & Co. KG). Hepatitis C inhibitor compounds. US 7585845.
【3】 Bhardwaj, P., Forgione, P., Goudreau, N. et al. (Boehringer Ingelheim International GmbH). Hepatitis C inhibitor compounds. EP 1654261, JP 2006528937, JP 2010043129, US 2005020503, US 2011177030, US 8067438, WO 2004103996.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	68434	methyl 8-bromo-4-hydroxy-7-methoxyquinoline-2-carboxylate		C₁₂H₁₀BrNO₄	详情	详情
(XXVI)	41985	2-amino-3-nitrophenol	603-85-0	C₆H₆N₂O₃	详情	详情
(XXVII)	68448	2-bromo-3-nitrophenol	101935-40-4	C₆H₄BrNO₃	详情	详情
(XXVIII)	68449	2-bromo-1-methoxy-3-nitrobenzene;2-Bromo-3-nitroanisole	67853-37-6	C₇H₆BrNO₃	详情	详情
(XXIX)	68451	2-bromo-3-methoxyaniline		C₇H₈BrNO	详情	详情
(XXX)	24551	Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester	762-42-5	C₆H₆O₄	详情	详情
(XXXI)	68450	dimethyl 2-((2-bromo-3-methoxyphenyl)amino)maleate		C₁₃H₁₄BrNO₅	详情	详情

Extended Information