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【结 构 式】

【分子编号】69113

【品名】1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone;4’-benzyloxy-5’-methoxy-2’-nitroacetophenone

【CA登记号】 

【 分 子 式 】C16H15NO5

【 分 子 量 】301.29884

【元素组成】C 63.78% H 5.02% N 4.65% O 26.55%

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:(XIX)

Treatment of cyclopropane-1,1-dicarboxylic acid (IX) with one equivalent of SOCl2 in the presence of Et3N in THF at 0 °C, followed by condensation of the activated intermediate with 4-fluoroaniline (X), provides the monoamide (XI) , which is optionally chlorinated to (VIII) by treatment with oxalyl chloride in cold THF .
Reaction of 3,4-difluoronitrobenzene (XII) with sodium benzylate prepared from benzyl alcohol and NaH in dimethylacetamide gives 1-benzyloxy-2-fluoro-4-nitrobenzene (XIII) as the main product. Subsequent reduction of compound (XIII) by means of iron and ammonium formate in refluxing toluene leads to the corresponding aniline (XIV), which is subsequently coupled with carboxylic acid (XI) using EDC in CH2Cl2 to afford the diamide (XV). Finally, debenzylation of diamide (XV) by transfer hydrogenation with 1,4-cyclohexadiene and Pd/C in boiling EtOH provides the target intermediate (I) . Scheme 2. Alternatively, acid chloride (VIII) can be directly condensed with 4-amino-2-fluorophenol (XVI) in the presence of 2,6-lutidine in cold THF to give diamide (I) .

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 Forsyth, T.P., Mac, M.B., Leahy, J.W., Nuss, J.M., Xu, W.(Exelixis, Inc.). c-Met modulators and methods of use. EP 1874759, JP 2008537748, US 2008161305, WO 2006108059.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 69103 7-(benzyloxy)-6-methoxyquinolin-4-yl trifluoromethanesulfonate   C18H14F3NO5S 详情 详情
(XVII) 22604 1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone 498-02-2 C9H10O3 详情 详情
(XVIII) 69112 1-(4-(benzyloxy)-3-methoxyphenyl)ethanone;3'-Methoxy-4'-(benzyloxy)acetophenone;4'-(Benzyloxy)-3'-methoxyacetophenone;Acetovanillone benzyl ether;1-(3-Methoxy-4-phenylmethoxyphenyl)ethanone 1835-11-6 C16H16O3 详情 详情
(XIX) 69113 1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone;4’-benzyloxy-5’-methoxy-2’-nitroacetophenone   C16H15NO5 详情 详情
(XX) 69114 1-(2-amino-4-(benzyloxy)-5-methoxyphenyl)ethanone   C16H17NO3 详情 详情
(XXI) 16602 ethyl formate 109-94-4 C3H6O2 详情 详情
(XXII) 67631 7-(benzyloxy)-6-methoxyquinolin-4-ol   C17H15NO3 详情 详情
Extended Information