|
【结 构 式】 
|
【分子编号】34660 【品名】diethyl 2-(2-ethoxyethyl)malonate 【CA登记号】 |
【 分 子 式 】C11H20O5 【 分 子 量 】232.2768 【元素组成】C 56.88% H 8.68% O 34.44% |
合成路线1
该中间体在本合成路线中的序号：(III)Diethyl malonate (I) was alkylated with 2-bromoethyl ethyl ether (II) in the presence of NaOEt to provide diethyl 2-(ethoxyethyl)malonate (III). Treatment of 2-chloronitrobenzene (IV) with 2,2,2-trifluoroethanol (V) afforded the trifluoroethyl ether (VI). Subsequent reduction of the nitro group of (VI) by means of iron in acetic acid gave aniline (VII), which was condensed with malonate (III) in refluxing diphenyl ether, yielding furoquinoline (VIII). Further reaction of (VIII) with o-toluidine (IX) in boiling diethylene glycol produced the tetrahydropyrroloquinoline (X). Aromatization of the pyrrole ring of (X) to give (XI) was achieved by dehydrogenation in diphenyl ether in the presence of Pd/C. Chloroquinoline (XII) was then obtained by chlorination of (XI) with POCl3. Finally, displacement of the chlorine atom of (XII) by means of ethanolamine at 180 C furnished the title compound.
| 【1】 Kim, H.-J.; Kim, S.-S.; Yoo, Y.-K.; Kang, S.-K.; Cheon, H.-G.; Choi, J.-K.; Yum, E.-K. (Korea Research Institute of Chemical Technology); Pyrrolo[3,2-c]quinoline derivs. containing haloalkoxy group and pharmaceutically acceptable salts thereof. CA 2268166; EP 0966466; JP 2000504352; US 6011044; WO 9909029 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 | |
| (I) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (II) | 34659 | 2-bromoethyl ethyl ether; 1-bromo-2-ethoxyethane | 592-55-2 | C4H9BrO | 详情 | 详情 |
| (III) | 34660 | diethyl 2-(2-ethoxyethyl)malonate | C11H20O5 | 详情 | 详情 | |
| (IV) | 15248 | 1-chloro-2-nitrobenzene | 88-73-3 | C6H4ClNO2 | 详情 | 详情 |
| (V) | 19483 | 2,2,2-trifluoro-1-ethanol | 75-89-8 | C2H3F3O | 详情 | 详情 |
| (VI) | 29562 | 2-nitrophenyl 2,2,2-trifluoroethyl ether; 1-nitro-2-(2,2,2-trifluoroethoxy)benzene | C8H6F3NO3 | 详情 | 详情 | |
| (VII) | 29563 | 2-(2,2,2-trifluoroethoxy)aniline; 2-(2,2,2-trifluoroethoxy)phenylamine | C8H8F3NO | 详情 | 详情 | |
| (VIII) | 34661 | 6-(2,2,2-trifluoroethoxy)-3,5-dihydrofuro[3,2-c]quinolin-4(2H)-one | C13H10F3NO3 | 详情 | 详情 | |
| (IX) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (X) | 34662 | 1-(2-methylphenyl)-6-(2,2,2-trifluoroethoxy)-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-c]quinolin-4-one | C20H17F3N2O2 | 详情 | 详情 | |
| (XI) | 34663 | 1-(2-methylphenyl)-6-(2,2,2-trifluoroethoxy)-1,5-dihydro-4H-pyrrolo[3,2-c]quinolin-4-one | C20H15F3N2O2 | 详情 | 详情 | |
| (XII) | 34664 | 4-chloro-1-(2-methylphenyl)-6-(2,2,2-trifluoroethoxy)-1H-pyrrolo[3,2-c]quinoline; 4-chloro-1-(2-methylphenyl)-1H-pyrrolo[3,2-c]quinolin-6-yl 2,2,2-trifluoroethyl ether | C20H14ClF3N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Reaction of 2-chloronitrobenzene (I) with the sodium alkoxide of 2,2,2-trifluoroethanol (II) in cold THF afforded trifluoroethyl ether (III). The nitro group of (III) was then reduced by means of iron and AcOH to produce 2-(trifluoroethoxy)aniline (IV). Condensation of (IV) with diethyl (2-ethoxyethyl)malonate (V) in boiling diphenyl ether led to the furoquinolinone system (VI), and subsequent reaction of (VI) with 2-methyl-4-methoxyaniline (VII) in refluxing diethylene glycol generated the pyrroloquinolinone (VIII). Chlorination of (VIII) with POCl3 gave chloropyrroloquinoline (IX). Finally, displacement of the chlorine of (IX) by ethanolamine at 180 C yielded the title compound.
| 【1】 Kim, H.-J.; Kim, S.-S.; Yoo, Y.-K.; Kang, S.-K.; Cheon, H.-G.; Choi, J.-K.; Yum, E.-K. (Korea Research Institute of Chemical Technology); Pyrrolo[3,2-c]quinoline derivs. containing haloalkoxy group and pharmaceutically acceptable salts thereof. CA 2268166; EP 0966466; JP 2000504352; US 6011044; WO 9909029 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 | |
| (I) | 15248 | 1-chloro-2-nitrobenzene | 88-73-3 | C6H4ClNO2 | 详情 | 详情 |
| (II) | 19483 | 2,2,2-trifluoro-1-ethanol | 75-89-8 | C2H3F3O | 详情 | 详情 |
| (III) | 29562 | 2-nitrophenyl 2,2,2-trifluoroethyl ether; 1-nitro-2-(2,2,2-trifluoroethoxy)benzene | C8H6F3NO3 | 详情 | 详情 | |
| (IV) | 29563 | 2-(2,2,2-trifluoroethoxy)aniline; 2-(2,2,2-trifluoroethoxy)phenylamine | C8H8F3NO | 详情 | 详情 | |
| (V) | 34660 | diethyl 2-(2-ethoxyethyl)malonate | C11H20O5 | 详情 | 详情 | |
| (VI) | 34661 | 6-(2,2,2-trifluoroethoxy)-3,5-dihydrofuro[3,2-c]quinolin-4(2H)-one | C13H10F3NO3 | 详情 | 详情 | |
| (VII) | 40006 | 4-methoxy-2-methylphenylamine; 4-methoxy-2-methylaniline | 102-50-1 | C8H11NO | 详情 | 详情 |
| (VIII) | 40007 | 1-(4-methoxy-2-methylphenyl)-6-(2,2,2-trifluoroethoxy)-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-c]quinolin-4-one | C21H19F3N2O3 | 详情 | 详情 | |
| (IX) | 40008 | 4-chloro-1-(4-methoxy-2-methylphenyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinolin-6-yl 2,2,2-trifluoroethyl ether; 4-chloro-1-(4-methoxy-2-methylphenyl)-6-(2,2,2-trifluoroethoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline | C21H18ClF3N2O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Diethyl malonate (I) was alkylated with 2-bromoethyl ethyl ether (II) to provide diethyl (2-ethoxyethyl)malonate (III). Subsequent condensation of malonate (III) with 2-(trifluoromethoxy)aniline (IV) in boiling diphenyl ether generated the furoquinoline derivative (V). This was then condensed with 2-methyl-4-methoxyaniline (VI) in refluxing diethylene glycol to furnish adduct (VII). Chlorination of pyrroloquinolone (VII) with phosphoryl chloride gave rise to the chloro pyrroloquinoline (VIII). The chloro group of (VIII) was finally displaced with ethanolamine (IX) at 190 C, yielding the title compound.
| 【1】 Kim, H.-J.; Kim, S.-S.; Yoo, Y.-K.; Kang, S.-K.; Cheon, H.-G.; Choi, J.-K.; Yum, E.-K. (Korea Research Institute of Chemical Technology); Pyrrolo[3,2-c]quinoline derivs. containing haloalkoxy group and pharmaceutically acceptable salts thereof. CA 2268166; EP 0966466; JP 2000504352; US 6011044; WO 9909029 . |
| 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) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (II) | 34659 | 2-bromoethyl ethyl ether; 1-bromo-2-ethoxyethane | 592-55-2 | C4H9BrO | 详情 | 详情 |
| (III) | 34660 | diethyl 2-(2-ethoxyethyl)malonate | C11H20O5 | 详情 | 详情 | |
| (IV) | 51625 | 2-trifluoromethoxyaniline; alpha,alpha,alpha-trifluoro-o-anisidine; o-trifluoromethoxyaniline | 1535-75-7 | C7H6F3NO | 详情 | 详情 |
| (V) | 51626 | 6-(trifluoromethoxy)-3,5-dihydrofuro[3,2-c]quinolin-4(2H)-one | C12H8F3NO3 | 详情 | 详情 | |
| (VI) | 40006 | 4-methoxy-2-methylphenylamine; 4-methoxy-2-methylaniline | 102-50-1 | C8H11NO | 详情 | 详情 |
| (VII) | 51627 | 1-(4-methoxy-2-methylphenyl)-6-(trifluoromethoxy)-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-c]quinolin-4-one | C20H17F3N2O3 | 详情 | 详情 | |
| (VIII) | 51628 | 4-chloro-1-(4-methoxy-2-methylphenyl)-6-(trifluoromethoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline; 4-chloro-1-(4-methoxy-2-methylphenyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinolin-6-yl trifluoromethyl ether | C20H16ClF3N2O2 | 详情 | 详情 | |
| (IX) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |