6-(2,2,2-trifluoroethoxy)-3,5-dihydrofuro[3,2-c]quinolin-4(2H)-one -Drug Synthesis Database

【结构式】

【分子编号】34661

【品名】6-(2,2,2-trifluoroethoxy)-3,5-dihydrofuro[3,2-c]quinolin-4(2H)-one

【CA登记号】

【分子式】C₁₃H₁₀F₃NO₃

【分子量】285.2225496

【元素组成】C 54.74% H 3.53% F 19.98% N 4.91% O 16.83%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【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：(VI)

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.

参考文献中间体

合成目标

【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

Extended Information