5-(2-aminoethyl)-2-methoxyphenol -Drug Synthesis Database

【结构式】

【分子编号】36471

【品名】5-(2-aminoethyl)-2-methoxyphenol

【CA登记号】

【分子式】C₉H₁₃NO₂

【分子量】167.20776

【元素组成】C 64.65% H 7.84% N 8.38% O 19.14%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXIII)

The esterification of the primary OH group of (XVIII) with the protected cysteine (XIX) by means of EDC and DMAP in dichloromethane gives ester (XX), which is cyclized by means of trifluoromethanesulfonic anhydride and DMSO yielding the bridged lactone (XXI). The oxidation of (XXI) with N-methylpyridinium-4-carbaldehyde (NMPA), DBU and PdCl2(PPh3)2 affords the oxolactone (XXII), which is finally cyclized with 2-(3-hydroxy-4-methoxyphenyl)ethylamine (XXIII) by means of TFA and AgNO3 in water.

参考文献中间体

合成目标

【1】 Gin, D.Y.; Corey, E.J.; Kania, R.S.; Enantioselective total synthesis of Ecteinascidin 743. J Am Chem Soc 1996, 118, 38, 9202-03.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVIII)	36466	(1R,2S,4R,13R,15R,16S)-4-hydroxy-13-(hydroxymethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-5-oxo-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-6,11,18,20,22-pentaene-15-carbonitrile	C₂₈H₃₃N₃O₈	详情	详情
(XIX)	36467	(2R)-2-[[(allyloxy)carbonyl]amino]-3-[(9H-fluoren-9-ylmethyl)sulfanyl]propionic acid	C₂₁H₂₁NO₄S	详情	详情
(XX)	36468		C₄₉H₅₂N₄O₁₁S	详情	详情
(XXI)	36469	(1R,2R,3R,11S,12R,14R)-26-[[(allyloxy)carbonyl]amino]-12-cyano-6-methoxy-5-(methoxymethoxy)-7,21,30-trimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1(3,11).0(2,13).0(4,9).0(15,23).0(16,20)]triaconta-4,6,8,15,20,22-hexaen-22-yl	C₃₇H₄₂N₄O₁₁S	详情	详情
(XXII)	36470	(1R,2R,3R,11S,12R,14R)-12-cyano-6-methoxy-5-(methoxymethoxy)-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1(3,11).0(2,13).0(4,9).0(15,23).0(16,20)]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₃H₃₅N₃O₁₀S	详情	详情
(XXIII)	36471	5-(2-aminoethyl)-2-methoxyphenol	C₉H₁₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

Intermediate (XVII) by a treatment with Zn and HOAc eliminates the Troc protecting group, giving the primary amine (XVIII). This compound by treatment with 4-formyl-1-methylpyridinium iodide (NMPC), DBU and oxalic acid in order to convert the nitrile group into an alcohol, provides compund (XIX), which is finally cyclized with 2-(3-hydroxy-4-methoxyphenyl)ethylamine (XX) by means of SiO2 / EtOH, followed treatment with and AgNO3 in acetonitrile/water.

参考文献中间体

合成目标

【1】 Cuevas, C.; Martin, M.J.; Perez, M.; et al.; Synthesis of ecteinascidin ET-743 and phathalascidin Pt-650 from cyanosafracin B. Org Lett 2000, 2, 16, 2545.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVII)	41790		C₃₄H₃₅Cl₃N₄O₁₀S	详情	详情
(XVIII)	41791	(1R,2R,3S,11R,12R,14R,26R)-26-amino-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1(3,11).0(2,13).0(4,9).0(15,23).0(16,20)]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₁H₃₄N₄O₈S	详情	详情
(XIX)	41792	(1R,2R,3S,11R,12S,14R,26R)-26-amino-5,12-dihydroxy-6-methoxy-7,21,30-trimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1(3,11).0(2,13).0(4,9).0(15,23).0(16,20)]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₀H₃₅N₃O₉S	详情	详情
(XX)	36471	5-(2-aminoethyl)-2-methoxyphenol	C₉H₁₃NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(LII)

The Pictet-Spengler cyclization of (LI) with 2-(3-hydroxy-4-methoxyphenyl)ethylamine (LII) by means of NaOAc in ethanol yields the spiro-tetrahydroisoquinoline (LIII). Finally, the nitrile group of (LIII) is treated with AgNO3 in acetonitrile/water to afford the target Ecteinascidin 743.

参考文献中间体

合成目标

【1】 Abe, M.; Yanagisawa, A.; Tohma, S.; Kan, T.; Fukuyama, T.; Endo, A.; Total synthesis of ecteinascidin 743. J Am Chem Soc 2002, 124, 23, 6552.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(LI)	58648	(1R,2R,3R,11S,12R,14R)-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₁H₃₁N₃O₉S	详情	详情
(LII)	36471	5-(2-aminoethyl)-2-methoxyphenol	C₉H₁₃NO₂	详情	详情
(LIII)	58649		C₄₀H₄₂N₄O₁₀S	详情	详情

Extended Information