phenyl (1S)-2-hydroxy-1-phenylethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】19663

【品名】phenyl (1S)-2-hydroxy-1-phenylethylcarbamate

【CA登记号】

【分子式】C₁₅H₁₅NO₃

【分子量】257.28904

【元素组成】C 70.02% H 5.88% N 5.44% O 18.66%

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：(XVI)

A synthesis of the (S)-enantiomer of the target compound has also been reported, starting from (S)-1-phenylethanolamine (XIV). Treatment with phenyl chloroformate (XV) and NaHCO3 yielded carbamate (XVI). Subsequent reaction of (XVI) with methanesulfonyl chloride and Et3N provided mesylate (XVII). The sulfonamide (XVIII) was prepared from sulfonyl chloride (VII) by treatment with ammonia gas in CH2Cl2. Condensation of this sulfonamide with mesylate (XVII) in the presence of NaH produced the chiral imidazolidinone (XIX). Finally, the target compound was obtained by condensation with 4-nitrobenzoyl chloride (XII), followed by reduction with H2 in the presence of Raney-Ni.

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
(VII)	19654	1-(2,2,2-trifluoroacetyl)-5-indolinesulfonyl chloride		C₁₀H₇ClF₃NO₃S	详情	详情
(XII)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(XIV)	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
(XV)	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(XVI)	19663	phenyl (1S)-2-hydroxy-1-phenylethylcarbamate		C₁₅H₁₅NO₃	详情	详情
(XVII)	19664	(2S)-2-[(phenoxycarbonyl)amino]-2-phenylethyl methanesulfonate		C₁₆H₁₇NO₅S	详情	详情
(XVIII)	19665	1-(2,2,2-trifluoroacetyl)-5-indolinesulfonamide		C₁₀H₉F₃N₂O₃S	详情	详情
(XIX)	19666	(4S)-1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-4-phenyl-2-imidazolidinone		C₁₇H₁₇N₃O₃S	详情	详情
(XX)	19667	(4S)-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：(VI)

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