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【结 构 式】

【分子编号】68691

【品名】3-fluoro-4-nitrophenol;2-Fluoro-4-hydroxy-1-nitrobenzene;4-Nitro-3-fluorophenol

【CA登记号】394-41-2

【 分 子 式 】C6H4FNO3

【 分 子 量 】157.10110

【元素组成】C 45.87% H 2.57% F 12.09% N 8.92% O 30.55%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

Chlorination of picolinic acid (I) with SOCl2 in the presence of DMF at 72 °C gives 4-chloropyridine-2-carbonyl chloride hydrochloride (II), which is then esterified with MeOH to afford the corresponding methyl ester (III). Aminolysis of ester (III) with methylamine in MeOH gives 4-chloro-N-methylpyridine-2-carboxamide (IV) , which can also be prepared by direct amidation of acid chloride (II) with methylamine in THF/MeOH or by Minisci reaction of 4-chloropyridine (V) with N-methylformamide (VI) in the presence of H2SO4, H2O2 and FeSO4·7H2O . Condensation of chloropicolinamide (IV) with 4-amino-3-fluorophenol (VII) –prepared by reduction of 3-fluoro-4-nitrophenol (VIII) by means of H2 and Pd/C in EtOAc– in the presence of t-BuOK in DMAc at 100 °C provides the 4-phenoxypyridine derivative (IX), which is finally coupled with 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene (X) in toluene .

1 Scott, W.J., Joel, R., Ridel, B. et al. (Bayer Healthcare LLC). omega-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors. US 2002042517.
2 Dumas, J., Lynch, M., Scott, W.J., Ladouceur, G., Wilhelm, S. (Bayer Pharmaceuticals Corp.). Diaryl ureas with kinase inhibiting activity. CA 2526617, EP 1636585, JP 200751103, US 2007020704, WO 2004113274.
3 Dumas, J., Wilhelm, S., Boyer, S., Riedl, B. (Bayer Pharmaceuticals Corp). Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions. EP 1663978, JP 2006528196, US 2005038080, WO 2005009961.
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) 29950 2-pyridinecarboxylic acid;picolinic acid;Pyridine-2-carboxylic acid 98-98-6 C6H5NO2 详情 详情
(II) 49908 4-chloropyridine-2-carbonyl chloride hydrochloride;(4-Chloro-2-pyridinecarbonyl Chloride Hydrochloride);4-Chloro-2-pyridinecarbonyl Chloride Hydrochlorid 51727-15-2 C6H3Cl2NO.HCl 详情 详情
(III) 68688 methyl 4-chloropicolinate hydrochloride   C7H6ClNO2.HCl 详情 详情
(IV) 49910 4-chloro-N-methyl-2-pyridinecarboxamide;4-chloro-N-methylpyridine-2-carboxamide;4-chloro-N-methylpicolinamide;4-Chloro-N-methylpicolinamide;2-(N-Methylcarbamoyl)-4-chloropyridine;4-Chloropyridine-2-carboxylicacid methylamide;N-Methyl-4-chloro-2-pyridinecarboxamide;N-Methyl-4-chloropicolinamide 220000-87-3 C7H7ClN2O 详情 详情
(V) 32889 4-chloropyridine 7379-35-3 C5H4ClN 详情 详情
(VI) 68689 N-methylformamide;Methylformamide;Monomethylformamide;N-Methylformimidic acid;N-Monomethylformamide 123-39-7 C2H5NO 详情 详情
(VII) 68690 4-amino-3-fluorophenol;3-Fluoro-4-aminophenol 399-95-1 C6H6FNO 详情 详情
(VIII) 68691 3-fluoro-4-nitrophenol;2-Fluoro-4-hydroxy-1-nitrobenzene;4-Nitro-3-fluorophenol 394-41-2 C6H4FNO3 详情 详情
(IX) 68692 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide;4-(4-amino-3- fluorophenoxy)-N-methyl-2-Pyridinecarboxamide;4-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide;4-(4-Amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide 757251-39-1 C13H12FN3O2 详情 详情
(X) 37868 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene; 4-chloro-3-(trifluoromethyl)phenyl isocyanate 327-78-6 C8H3ClF3NO 详情 详情
Extended Information