N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine -Drug Synthesis Database

【结构式】

【分子编号】30528

【品名】N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine

【CA登记号】

【分子式】C₁₆H₁₉NO₂

【分子量】257.3324

【元素组成】C 74.68% H 7.44% N 5.44% O 12.43%

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：(III)

This compound has been obtained in two related ways: 1. The reaction of 2-(2-bromoethoxy)anisole (I) with benzylamine (II) by heating at 80 C gives the secondary amine (III), which is condensed with epichlorohydrin (IV) by heating at 60 C to yield the isopropanol derivative (V). The condensation of (V) with 4-hydroxycarbazole (VI) by means of K2CO3 in refluxing dioxane affords the adduct (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in ethanol/water. 2. The condensation of the secondary amine (III) with 4-(2,3-epoxypropoxy)carbazole (VIII) in refluxing ethanol gives the already reported adduct (VII), which is debenzylated as indicated.

参考文献中间体

合成目标

【1】 Seres, P.; Cselenyak, J.; Nagy, K.; Simig, G.; Gregor, T.; Nagy, P.K.; Greff, Z.; Balazs, L.; Barkoczy, J.; Vereczkey, G.D.; Nemeth, N.; Szabo, T.; Ratkai, Z.; Doman, I. (Egis Pharmaceuticals Ltd.); Process and intermediates for preparing 1-[9'H-carbazol-4'-yloxy]-3-[2''-(2'''-methoxy-phenoxy)ethyl]amino]-propan-2-ol (carvedilol). EP 0918055 .

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)	51402	2-(2-Bromoethoxy)methoxybenzene; 1-Bromo-2-(2-methoxyphenoxy)ethane	4463-59-6	C₉H₁₁BrO₂	详情	详情
(II)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(III)	30528	N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine		C₁₆H₁₉NO₂	详情	详情
(IV)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(V)	51403	1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-chloro-2-propanol		C₁₉H₂₄ClNO₃	详情	详情
(VI)	29480	4-Hydroxycarbazole; 9H-carbazol-4-ol	52602-39-8	C₁₂H₉NO	详情	详情
(VII)	51404	1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-(9H-carbazol-4-yloxy)-2-propanol		C₃₁H₃₂N₂O₄	详情	详情
(VIII)	40171	9H-carbazol-4-yl 2-oxiranylmethyl ether; 4-(2-oxiranylmethoxy)-9H-carbazole	51997-51-4	C₁₅H₁₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The condensation of 2-methoxyphenol (I) with ethylene oxide (II) gives 2-(2-methoxyphenoxy)ethanol (III), which is treated with SOCl2 to yield 2-(2-methoxyphenoxy)ethyl chloride (IV). The reaction of (IV) with benzylamine (A) gives N-[2-(2-methoxyphenoxy)ethyl]benzylamine (V), which is condensed with 2-methyl-5-bromoacetylbenzenesulfonamide (VI) affording N-[2-(2-methoxyphenoxy)ethyl]-N-[(4-methyl-3-aminosulfonylbenzoyl)methyl]benzylamine (VII). The reduction of (VII) with NaBH4 affords the corresponding protected carbinol (VIII), which is finally debenzylated by hydrogenation with H2 over Pd/C.

参考文献中间体

合成目标

【1】 Arima, H.; Tamazawa, K.; Synthesis of 14C-labeled 5-[1-hydroxy-2-[2-(o-methoxyphenoxy)ethylamino]ethyl]-2-methylbenzenesulfonamide hydochloride (YM-09538). J Label Compd Radiopharm 1983, 20, 7, 803-811.
【2】 Fujikura, T.; et al. (Yamanouchi Pharmaceutical Co., Ltd.); Phenylethanolamine derivatives. DE 2843016; ES 474149; ES 481549; FR 2405931; GB 2006772 .
【3】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Leeson, P.A.; Mealy, N.E.; YM-09,538. Drugs Fut 1981, 6, 7, 425.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(I)	13182	Guaiacol; 2-Methoxyphenol	90-05-1	C₇H₈O₂	详情	详情
(II)	10393	Oxirane; Ethylene oxide	75-21-8	C₂H₄O	详情	详情
(III)	30526	2-(2-methoxyphenoxy)-1-ethanol		C₉H₁₂O₃	详情	详情
(IV)	30527	2-(2-chloroethoxy)phenyl methyl ether; 1-(2-chloroethoxy)-2-methoxybenzene		C₉H₁₁ClO₂	详情	详情
(V)	30528	N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine		C₁₆H₁₉NO₂	详情	详情
(VI)	30529	5-(2-bromoacetyl)-2-methylbenzenesulfonamide		C₉H₁₀BrNO₃S	详情	详情
(VII)	30530	5-(2-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]acetyl)-2-methylbenzenesulfonamide		C₂₅H₂₈N₂O₅S	详情	详情
(VIII)	30531	5-(2-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-1-hydroxyethyl)-2-methylbenzenesulfonamide		C₂₅H₃₀N₂O₅S	详情	详情

Extended Information