1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone -Drug Synthesis Database

【结构式】

【分子编号】27861

【品名】1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone

【CA登记号】

【分子式】C₁₁H₁₀F₄N₂O₂

【分子量】278.2062928

【元素组成】C 47.49% H 3.62% F 27.32% N 10.07% O 11.5%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(V)

Aniline (I) was converted to phenyl carbamate (II) by treatment with phenyl chloroformate. Subsequent condensation of (III) with 2,2-diethoxyethylamine provided urea (III), which was cyclized under acidic conditions to give imidazolone (IV). Optionally, imidazolidinone (V) was obtained by catalytic hydrogenation of (IV).

参考文献中间体

合成目标

【1】 Itoh, K.; Tamura, N.; Matsushita, Y.; Hososno, H.; Hayashi, R.; Okonogi, K.; Kitazaki, T.; Tasaka, A.; Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones. Chem Pharm Bull 1999, 47, 3, 351.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(I)	27857	4-(1,1,2,2-tetrafluoroethoxy)aniline	713-62-2	C₈H₇F₄NO	详情	详情
(II)	27858	phenyl 4-(1,1,2,2-tetrafluoroethoxy)phenylcarbamate		C₁₅H₁₁F₄NO₃	详情	详情
(III)	27859	N-(2,2-diethoxyethyl)-N'-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]urea		C₁₅H₂₀F₄N₂O₄	详情	详情
(IV)	27860	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₁₁H₈F₄N₂O₂	详情	详情
(V)	27861	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₁₁H₁₀F₄N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Treatment of epoxyalcohol (XI) with trifluoromethanesulfonic anhydride and diisopropyl ethylamine gave triflate (XII). Condensation of (XII) with imidazolone (IV) provided the required N-alkylated compound (XIII) along with some O-alkylated isomer, which were separated by column chromatography. Epoxide opening with triazole (XIV) afforded the imidazolone (XV), which was finally hydrogenated to produce the target imidazolidinone. Alternatively, condensation of triflate (XII) with imidazolidinone (V) furnished, after chromatographic separation of some O-alkylated isomer, imidazolidinone (XVI). Finally, the reaction of (XVI) with triazole (XIV) then provided an alternative route to the tiarget compound.

参考文献中间体

合成目标

【1】 Itoh, K.; Tamura, N.; Matsushita, Y.; Hososno, H.; Hayashi, R.; Okonogi, K.; Kitazaki, T.; Tasaka, A.; Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones. Chem Pharm Bull 1999, 47, 3, 351.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	27860	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₁₁H₈F₄N₂O₂	详情	详情
(V)	27861	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₁₁H₁₀F₄N₂O₂	详情	详情
(XI)	27877	(1S)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]-1-ethanol		C₁₀H₁₀F₂O₂	详情	详情
(XII)	27878	(1S)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]ethyl trifluoromethanesulfonate		C₁₁H₉F₅O₄S	详情	详情
(XIII)	27879	1-[(1R)-1-[(2S)-2-(2,4-difluorophenyl)oxiranyl]ethyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₂₁H₁₆F₆N₂O₃	详情	详情
(XIV)	27880	1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₂₃H₁₉F₆N₅O₃	详情	详情
(XV)	13135	1H-1,2,4-Triazole; 1,2,4-Triazole	288-88-0	C₂H₃N₃	详情	详情
(XVI)	27881	1-[(1R)-1-[(2S)-2-(2,4-difluorophenyl)oxiranyl]ethyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₂₁H₁₈F₆N₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Aniline (I) was converted to phenyl carbamate (II) by treatment with phenyl chloroformate. Subsequent condensation of (II) with 2,2-diethoxyethylamine provided urea (III), which was cyclized under acidic conditions to give imidazolone (IV). Optionally, imidazolidinone (V) was obtained by catalytic hydrogenation of (IV).

参考文献中间体

合成目标

【1】 Itoh, K.; Tamura, N.; Matsushita, Y.; Hososno, H.; Hayashi, R.; Okonogi, K.; Kitazaki, T.; Tasaka, A.; Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones. Chem Pharm Bull 1999, 47, 3, 351.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(I)	27857	4-(1,1,2,2-tetrafluoroethoxy)aniline	713-62-2	C₈H₇F₄NO	详情	详情
(II)	27858	phenyl 4-(1,1,2,2-tetrafluoroethoxy)phenylcarbamate		C₁₅H₁₁F₄NO₃	详情	详情
(III)	27859	N-(2,2-diethoxyethyl)-N'-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]urea		C₁₅H₂₀F₄N₂O₄	详情	详情
(IV)	27860	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₁₁H₈F₄N₂O₂	详情	详情
(V)	27861	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₁₁H₁₀F₄N₂O₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

Treatment of epoxyalcohol (IX) with trifluoromethanesulfonic anhydride and diisopropyl ethylamine gave triflate (XIII). Condensation of (XIII) with imidazolone (IV) provided the required N-alkylated compound (XIV) along with some O-alkylated isomer, which were separated by column chromatography. Epoxide opening with triazole (XV) afforded the imidazolone (XVI), which was finally hydrogenated to produce the target imidazolidinone. Alternatively, condensation of triflate (XIII) with imidazolidinone (V) furnished, after chromatographic separation of some O-alkylated isomer, imidazolidinone (XVII). Finally, the reaction of (XVII) with triazole (XV) then provided an alternative route to the target compound.

参考文献中间体

合成目标

【1】 Itoh, K.; Tamura, N.; Matsushita, Y.; Hososno, H.; Hayashi, R.; Okonogi, K.; Kitazaki, T.; Tasaka, A.; Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones. Chem Pharm Bull 1999, 47, 3, 351.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	27860	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₁₁H₈F₄N₂O₂	详情	详情
(V)	27861	1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₁₁H₁₀F₄N₂O₂	详情	详情
(IX)	27865	(1S)-1-[(2R)-2-(2-fluorophenyl)oxiranyl]-1-ethanol		C₁₀H₁₁FO₂	详情	详情
(XIII)	27869	(1S)-1-[(2R)-2-(2-fluorophenyl)oxiranyl]ethyl trifluoromethanesulfonate		C₁₁H₁₀F₄O₄S	详情	详情
(XIV)	27870	1-[(1R)-1-[(2S)-2-(2-fluorophenyl)oxiranyl]ethyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₂₁H₁₇F₅N₂O₃	详情	详情
(XV)	13135	1H-1,2,4-Triazole; 1,2,4-Triazole	288-88-0	C₂H₃N₃	详情	详情
(XVI)	27871	1-[(1R,2R)-2-(2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-1,3-dihydro-2H-imidazol-2-one		C₂₃H₂₀F₅N₅O₃	详情	详情
(XVII)	27872	1-[(1R)-1-[(2S)-2-(2-fluorophenyl)oxiranyl]ethyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-imidazolidinone		C₂₁H₁₉F₅N₂O₃	详情	详情

Extended Information