1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】19653

【品名】1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone

【CA登记号】

【分子式】C₁₀H₈F₃NO

【分子量】215.1748696

【元素组成】C 55.82% H 3.75% F 26.49% N 6.51% O 7.44%

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：(VI)

The bromination of styrene (II) with N-bromosuccinimide in the presence of cyanamide (I) provided 2-bromo-1-phenylethylcyanamide (III). Further addition of MeOH to (III) in the presence of HCl, followed by Na2CO3-promoted cyclization, produced the methoxyimidazoline (IV). Acylation of indoline (V) with trifluoroacetic anhydride and pyridine gave amide (VI) and subsequent chlorosulfonation yielded sulfonyl cloride (VII). This acid chloride was coupled to imidazoline (IV) in the presence of NaHCO3 in aqueous acetone to furnish a mixture of sulfonyl imidazolines (VIII) and (IX). The major isomer (IX) was isolated by column chromatography, and then, hydrolysis with HCl in MeOH at r.t. provided imidazolidinone (X). The trifluoroacetamide group of (X) was further hydrolyzed by treatment with NaOH in aqueous MeOH to give (XI). Subsequent condensation of (XI) with 4-nitrobenzoyl chloride (XII) in the presence of pyridine yielded 4-nitrobenzamide (XIII), which was finally reduced to the aminobenzamide by hydrogenation using Raney-nickel as the catalyst.

参考文献中间体

合成目标

【1】 Jung, S.-H.; Lee, H.S.; Song, J.S.; Kim, H.M.; Han, S.B.; Lee, C.W.; Lee, M.; Choi, D.R.; Lee, J.A.; Chung, Y.H.; Yoon, S.J.; Moon, E.Y.; Hwang, H.S.; Seong, S.K.; Lee, D.K.; Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones. Bioorg Med Chem Lett 1998, 8, 12, 1547.
【2】 Yoon, S.J.; Chung, Y.H.; Lee, M.S.; Choi, D.R.; Lee, J.A.; Lee, H.S.; Yun, H.R.; Lee, D.K.; Moon, E.Y.; Hwang, H.S.; Choi, C.H.; Jung, S.H. (Dong-Wha Pharmaceuticals Industry Co. Ltd); Arylsulfonylimidazolone derivs. as an antitumor agent. EP 1021437; JP 2000505096; US 5929103; WO 9807719 .

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)	19648	Cyanamide	420-04-2	CH₂N₂	详情	详情
(II)	19649	1-vinylbenzene	100-42-5	C₈H₈	详情	详情
(III)	19650	2-bromo-1-phenylethylcyanamide		C₉H₉BrN₂	详情	详情
(IV)	19651	methyl 5-phenyl-4,5-dihydro-1H-imidazol-2-yl ether; 2-methoxy-5-phenyl-4,5-dihydro-1H-imidazole		C₁₀H₁₂N₂O	详情	详情
(V)	19652	indoline	496-15-1	C₈H₉N	详情	详情
(VI)	19653	1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone		C₁₀H₈F₃NO	详情	详情
(VII)	19654	1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride		C₁₀H₇ClF₃NO₃S	详情	详情
(VIII)	19655	2,2,2-trifluoro-1-[5-[(2-methoxy-5-phenyl-4,5-dihydro-1H-imidazol-1-yl)sulfonyl]-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₂₀H₁₈F₃N₃O₄S	详情	详情
(IX)	19656	2,2,2-trifluoro-1-[5-[(2-methoxy-4-phenyl-4,5-dihydro-1H-imidazol-1-yl)sulfonyl]-2,3-dihydro-1H-indol-1-yl]-1-ethanone		C₂₀H₁₈F₃N₃O₄S	详情	详情
(X)	19657	4-phenyl-1-[[1-(2,2,2-trifluoroacetyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-2-imidazolidinone		C₁₉H₁₆F₃N₃O₄S	详情	详情
(XI)	19658	1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone		C₁₇H₁₇N₃O₃S	详情	详情
(XII)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(XIII)	19660	1-[[1-(4-nitrobenzoyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-phenyl-2-imidazolidinone		C₂₄H₂₀N₄O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Protection of indoline (I) using trifluoroacetic anhydride provided N-trifluoroacetylindoline (II), which was sulfonated with chlorosulfonic acid to give sulfonyl chloride (III). Further treatment with ammonia in CH2Cl2 produced sulfonamide (IV). Phenylglycinol (V) was condensed with phenyl chloroformate to afford carbamate (VI). Subsequent reaction of (VI) with metanesulfonyl chloride and triethylamine yielded mesylate (VII). The condensation of sulfonamide (IV) with mesylate (VII), with concomitant cyclization of carbamate group and trifluoroacetyl deprotection, furnished imidazolone (VIII). This was further condensed with 4-nitrobenzoyl chloride (IX), and the resulting 4-nitrobenzamide (X) was finally reduced to the target aminobenzamide by hydrogenation over Raney Nickel.

参考文献中间体

合成目标

【1】 Yoon, S.J.; Chung, Y.H.; Lee, M.S.; Choi, D.R.; Lee, J.A.; Lee, H.S.; Yun, H.R.; Lee, D.K.; Moon, E.Y.; Hwang, H.S.; Choi, C.H.; Jung, S.H. (Dong-Wha Pharmaceuticals Industry Co. Ltd); Arylsulfonylimidazolone derivs. as an antitumor agent. EP 1021437; JP 2000505096; US 5929103; WO 9807719 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(I)	19652	indoline	496-15-1	C₈H₉N	详情	详情
(II)	19653	1-(2,3-dihydro-1H-indol-1-yl)-2,2,2-trifluoro-1-ethanone		C₁₀H₈F₃NO	详情	详情
(III)	19654	1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride		C₁₀H₇ClF₃NO₃S	详情	详情
(IV)	19665	1-(2,2,2-trifluoroacetyl)-5-indolinesulfonamide		C₁₀H₉F₃N₂O₃S	详情	详情
(V)	10973	(2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol	20989-17-7	C₈H₁₁NO	详情	详情
(VI)	19663	phenyl (1S)-2-hydroxy-1-phenylethylcarbamate		C₁₅H₁₅NO₃	详情	详情
(VII)	19664	(2S)-2-[(phenoxycarbonyl)amino]-2-phenylethyl methanesulfonate		C₁₆H₁₇NO₅S	详情	详情
(VIII)	19666	(4S)-1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone		C₁₇H₁₇N₃O₃S	详情	详情
(IX)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(X)	19667	(4S)-1-[[1-(4-nitrobenzoyl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]-4-phenyl-2-imidazolidinone		C₂₄H₂₀N₄O₆S	详情	详情

Extended Information