【结 构 式】 |
【分子编号】67674 【品名】ethyl 6-hydroxy-1-naphthoate 【CA登记号】 |
【 分 子 式 】C13H12O3 【 分 子 量 】216.23648 【元素组成】C 72.21% H 5.59% O 22.2% |
合成路线1
该中间体在本合成路线中的序号:(XLIII)Activation of 6-hydroxy-1-naphthoic acid (I) using CDI, followed by coupling with methylamine hydrochloride (III) in DMF at 90 °C gives amide (V). Condensation of compound (V) with the aryl chloride (VI) using DMAP in 2,6-lutidine or i-PrOH at 130 °C or by means of Cs2CO3, CuI and picolinic acid or acetylacetone (Ullmann reaction) in DMF at 120 °C affords the diaryl ether (VIII), whose benzyl group is finally cleaved using TFA at 90 °C .
Esterification naphthoic acid (I) with EtOH and H2SO4 at reflux yields ethyl 6-hydroxy-1-naphthoic acid (XLIII), which then couples with aryl chloride (VI) in the presence of DMAP in 2,6-lutidine or i-PrOH at 130°C or by means of Cs2CO3, CuI and picolinic acid or acetylacetone in DMF at 120 °C (Ullmann reaction) to give diayl ether (XLIV). Finally, this compound is debenzylated with TFA at 90 °C .
【1】 Chen, G.P. (Advenchen Laboratories, LLC). Process for preparing the antitumor agent 6-(7-((1-aminocyclopropyl) methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide and its crystalline. WO 2014113616. |
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) | 67625 | 6-hydroxy-1-naphthoic acid;6-Hydroxy-1-naphthalenecarboxylic acid | 2437-17-4 | C11H8O3 | 详情 | 详情 |
(III) | 67627 | methanamine hydrochloride | CH5N.HCl | 详情 | 详情 | |
(V) | 67629 | 6-hydroxy-N-methyl-1-naphthamide | C12H11NO2 | 详情 | 详情 | |
(VI) | 67630 | 7-benzyloxy-6-methoxy-4-chloroquinoline | C17H14ClNO2 | 详情 | 详情 | |
(VIII) | 67632 | 6-((7-(benzyloxy)-6-methoxyquinolin-4-yl)oxy)-N-methyl-1-naphthamide | C29H24N2O4 | 详情 | 详情 | |
(IX) | 67633 | 6-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)-N-methyl-1-naphthamide | C22H18N2O4 | 详情 | 详情 | |
(XL) | 67670 | ethyl 6-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)-1-naphthoate | C23H19NO5 | 详情 | 详情 | |
(XLIII) | 67674 | ethyl 6-hydroxy-1-naphthoate | C13H12O3 | 详情 | 详情 | |
(XLIV) | 67675 | ethyl 6-((7-(benzyloxy)-6-methoxyquinolin-4-yl)oxy)-1-naphthoate | C30H25NO5 | 详情 | 详情 |