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【结 构 式】

【分子编号】49909

【品名】methyl 4-chloro-2-pyridinecarboxylate

【CA登记号】24484-93-3

【 分 子 式 】C7H6ClNO2

【 分 子 量 】171.58288

【元素组成】C 49% H 3.52% Cl 20.66% N 8.16% O 18.65%

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:(III)

Reaction of picolinic acid (I) with hot thionyl chloride in DMF gives 4-chloropyridine-2-carbonyl chloride (II), which is treated with methanol to give ester (III). Subsequent displacement of the methyl ester function with methylamine provides amide (IV). Alternatively, acid chloride (II) is directly converted into amide (IV) by reaction with a cold solution of methylamine. In a different synthetic procedure, amide (IV) can be obtained from 4-chloropyridine (V) via the Menisci reaction using N-methylformamide and hydrogen peroxide in the presence of FeSO4 and H2SO4. Coupling of the amide (IV) with potassium 4-aminophenolate (VI) -obtained by treatment of 4-aminophenol (VII) with potassium tert-butoxide- in hot DMF yields the pyridyloxyaniline (VIII). Aniline (VIII) is finally condensed with either 4-chloro-3-(trifluoromethyl)phenyl isocyanate (IX) in CH2Cl2 or 4-chloro-3-(trifluoromethyl)aniline (X) by means of CDI in CH2Cl2.

1 Sorbera, L.A.; Castaner, J.; Bozzo, J.; Leeson, P.A.; BAY-43-9006. Drugs Fut 2002, 27, 12, 1141.
2 Monahan, M.-K.; Sibley, R.; Natero, R.; Dumas, J.; Bankston, D.; Riedl, B.; A scaleable synthesis of BAY 43-9006: A potent Raf kinase inhibitor for the treatment of cancer. Org Process Res Dev 2002, 6, 6, 777.
3 Smith, R.A.; Monahan, M.-K.; Riedl, B.; Scott, W.J.; Khire, U.; Lowinger, T.B.; Natero, R.; Sibley, R.N.; Wood, J.E.; Renick, J.; Dumas, J. (Bayer Corp.); omega-Carboxy aryl substd. diphenyl ureas as p38 kinase inhibitors. WO 0041698 .
4 Lowinger, T.B.; Monahan, M.-K.; Dumas, J.; Scott, W.J.; Khire, U.; Wood, J.E.; Renick, J.; Riedl, B.; Smith, R.A.; Natero, R.; Sibley, R.N. (Bayer Corp.); omega-Carboxyaryl substd. diphenyl ureas as raf kinase inhibitors. EP 1140840; WO 0042012 .
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) 49909 methyl 4-chloro-2-pyridinecarboxylate 24484-93-3 C7H6ClNO2 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) 49911 potassium 4-aminobenzenolate C6H6KNO 详情 详情
(VII) 49912 4-(4-aminophenoxy)-N-methyl-2-pyridinecarboxamide 284462-37-9 C13H13N3O2 详情 详情
(VII) 49912 4-(4-aminophenoxy)-N-methyl-2-pyridinecarboxamide 284462-37-9 C13H13N3O2 详情 详情
(VIII) 37868 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene; 4-chloro-3-(trifluoromethyl)phenyl isocyanate 327-78-6 C8H3ClF3NO 详情 详情
Extended Information