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【结 构 式】

【分子编号】69108

【品名】cyclopropane-1,1-dicarboxylic acid

【CA登记号】 

【 分 子 式 】C5H6O4

【 分 子 量 】130.10024

【元素组成】C 46.16% H 4.65% O 49.19%

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:(IX)

a) Condensation of the phenolic compound (I) with 7-benzyloxy-6-methoxyquinolinyl triflate (II) in refluxing 2,6-lutidine affords the quinolinyl ether (III), which is O-debenzylated by transfer hydrogenation with 1,4-cyclohexadiene and Pd/C in EtOH at 65 °C, producing the 7-hydroxyquinoline derivative (IV). Finally, the hydroxyquinoline (IV) is alkylated with N-(3-chloropropyl)morpholine hydrochloride (V) by means of K2CO3 in DMF at 90 °C .
b) Direct coupling of the phenol derivative (I) with 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline (VI) in the presence of Pd(OAc)2, 2-(di-tert-butylphosphino)-1,1’-binaphthyl (DTBPB) and K3PO4 in anisole at 110 °C or NMP/toluene at 95 °C .
c) Acylation of the quinolinyloxyaniline intermediate (VII) with 1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl chloride (VIII) by means of K2CO3 in THF/H2O .

1 Bannen, L.C., Chan, D.S.-M., Chen, J. (Exelixis, Inc.). c-Met modulators and methods of use. EP 1673085, EP 2210607, EP 2213661, JP 2007506777, JP 2010235631, JP 2010235632, WO 2005030140.
2 Deschamps, N.M., Martin, M.T., Monteith, M.J., Zhou, X. (GlaxoSmithKline Inc.). Preparation of a quinolinyloxydiphenylcyclopropanedicarboxamide. US 2010081805, WO 010036831.
3 Wilson, J., Zuberi, S., Naganathan, S., Goldman, E., Kanter, J. (Exelixis, Inc.). Methods of preparing quinoline derivatives. WO 2010056960.
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) 69100 N-(3-fluoro-4-hydroxyphenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide   C17H14F2N2O3 详情 详情
(VIII) 69107 1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl chloride   C11H9ClFNO2 详情 详情
(IX) 69108 cyclopropane-1,1-dicarboxylic acid   C5H6O4 详情 详情
(X) 37690 4-fluorophenylamine; 4-fluoroaniline 371-40-4 C6H6FN 详情 详情
(XI) 69109 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid   C11H10FNO3 详情 详情
(XII) 17013 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene 369-34-6 C6H3F2NO2 详情 详情
(XIII) 67754 1-benzyloxy-2-fluoro-4-nitrobenzene;1-(benzyloxy)-2-fluoro-4-nitrobenzene   C13H10FNO3 详情 详情
(XIV) 67755 4-benzyloxy-3-fluoroaniline   C13H12FNO 详情 详情
(XV) 69110 N-(4-(benzyloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide   C24H20F2N2O3 详情 详情
(XVI) 69111 4-amino-2-fluorophenol;2-Fluoro-4-aminophenol 399-96-2 C6H6FNO 详情 详情
Extended Information