ethyl 2-[3-{[(1S)-2-amino-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate -Drug Synthesis Database

【结构式】

【分子编号】64206

【品名】ethyl 2-[3-{[(1S)-2-amino-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate

【CA登记号】

【分子式】C₁₇H₂₁ClN₄O₃

【分子量】364.8316

【元素组成】C 55.97% H 5.8% Cl 9.72% N 15.36% O 13.16%

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：(XIII)

Mitsunobu coupling of N-Boc-L-phenylglycinol (VIII) with hydrazoic acid affords azide (IX). Subsequent acidic cleavage of the N-Boc protecting group of (IX) furnishes amino azide (X). This is then condensed with the bromopyrazinone (VII) upon heating at 110 C in a pressure vessel to furnish adduct (XI). Treatment of (XI) with N-chlorosuccinimide in hot dichloroethane gives rise to the chloropyrazinone (XII). The azido group of (XII) is then reduced to the corresponding amine (XIII) employing SnCl2 in MeOH/THF (1,2).

参考文献中间体

合成目标

【1】 Nantermet, P.G.; Barrow, J.C.; Newton, C.L.; Pellicore, J.M.; Young, M.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; McMasters, D.R.; Youwei, Y.; Kuo, L.C.; Vacca, J.P.; Selnick, H.G.; Design and synthesis of potent and selective macrocyclic thrombin inhibitors. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 168.
【2】 Selnick, H.G.; Newton, R.C.; Newton, C.L.; Barrow, J.C.; Nantermet, P.G. (Merck & Co., Inc.); Thrombin inhibitors. WO 0311222 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VII)	63219	ethyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate	C₈H₉BrN₂O₃	详情	详情
(VIII)	54624	tert-butyl (1S)-1-benzyl-2-hydroxyethylcarbamate	C₁₄H₂₁NO₃	详情	详情
(IX)	63851	tert-butyl (1S)-2-azido-1-benzylethylcarbamate	C₁₄H₂₀N₄O₂	详情	详情
(X)	63852	(1S)-2-azido-1-benzylethylamine; (2S)-1-azido-3-phenyl-2-propanamine	C₉H₁₂N₄	详情	详情
(XI)	64204	ethyl 2-[3-{[(1S)-2-azido-1-benzylethyl]amino}-2-oxo-1(2H)-pyrazinyl]acetate	C₁₇H₂₀N₆O₃	详情	详情
(XII)	64205	ethyl 2-[3-{[(1S)-2-azido-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₁₇H₁₉ClN₆O₃	详情	详情
(XIII)	64206	ethyl 2-[3-{[(1S)-2-amino-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₁₇H₂₁ClN₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Reductive condensation between aldehyde (XXV) and amine (XIII) in the presence of NaBH(OAc)3 leads to adduct (XXX). The N-Boc protecting groups of (XXX) are then cleaved under acidic conditions yielding tetra-amine (XXXI). Saponification of the ethyl ester group of (XXXI) with LiOH furnishes amino acid (XXXII). Finally, the title compound is obtained by macrocyclization of (XXXII) employing EDC/HOAt as the coupling reagent (1,2).

参考文献中间体

合成目标

【1】 Nantermet, P.G.; Barrow, J.C.; Newton, C.L.; Pellicore, J.M.; Young, M.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; McMasters, D.R.; Youwei, Y.; Kuo, L.C.; Vacca, J.P.; Selnick, H.G.; Design and synthesis of potent and selective macrocyclic thrombin inhibitors. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 168.
【2】 Selnick, H.G.; Newton, R.C.; Newton, C.L.; Barrow, J.C.; Nantermet, P.G. (Merck & Co., Inc.); Thrombin inhibitors. WO 0311222 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	64206	ethyl 2-[3-{[(1S)-2-amino-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₁₇H₂₁ClN₄O₃	详情	详情
(XXV)	64217	tert-butyl 2-{[(tert-butoxycarbonyl)amino]methyl}phenethyl(3-oxopropyl)carbamate	C₂₂H₃₄N₂O₅	详情	详情
(XXX)	64221	ethyl 2-[3-{[(1S)-1-benzyl-2-({3-[(tert-butoxycarbonyl)(2-{[(tert-butoxycarbonyl)amino]methyl}phenethyl)amino]propyl}amino)ethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₃₉H₅₅ClN₆O₇	详情	详情
(XXXI)	64222	ethyl 2-[3-({(1S)-2-[(3-{[2-(aminomethyl)phenethyl]amino}propyl)amino]-1-benzylethyl}amino)-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₂₉H₃₉ClN₆O₃	详情	详情
(XXXII)	64223	2-[3-({(1S)-2-[(3-{[2-(aminomethyl)phenethyl]amino}propyl)amino]-1-benzylethyl}amino)-6-chloro-2-oxo-1(2H)-pyrazinyl]acetic acid	C₂₇H₃₅ClN₆O₃	详情	详情

Extended Information