propyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate -Drug Synthesis Database

【结构式】

【分子编号】63820

【品名】propyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate

【CA登记号】

【分子式】C₉H₁₁BrN₂O₃

【分子量】275.10202

【元素组成】C 39.29% H 4.03% Br 29.05% N 10.18% O 17.45%

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：(VII)

The bromo pyrazinone intermediate (VII) has been obtained as follows. The condensation of ethyl glycinate (I) with ethoxalyl chloride (II) by means of TEA in dichloroethane gives the corresponding amide (III), which is condensed with aminoacetaldehyde dimethyl acetal (IV) in isopropanol to yield the diamide (V). The cyclization of (V) by means of HCl in refluxing AcOH affords the hydroxypyrazinone (VI), which is finally treated with POBr3 in refluxing 1,2-dichloroethane to provide the target bromopyrazinone intermediate (VII) (1).

参考文献中间体

合成目标

【1】 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	CAS号	分子式	供应商	用于合成
(I)	11043	Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride	4755-77-5	C₄H₅ClO₃	详情	详情
(II)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(III)	63817	ethyl 2-oxo-2-[(2-oxo-2-propoxyethyl)amino]acetate		C₉H₁₅NO₅	详情	详情
(IV)	34158	aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine	22483-09-6	C₄H₁₁NO₂	详情	详情
(V)	63818	propyl 2-({2-[(2,2-dimethoxyethyl)amino]-2-oxoacetyl}amino)acetate		C₁₁H₂₀N₂O₆	详情	详情
(VI)	63819	propyl 2-[3-hydroxy-2-oxo-1(2H)-pyrazinyl]acetate		C₉H₁₂N₂O₄	详情	详情
(VII)	63820	propyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate		C₉H₁₁BrN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The reaction of N-(2(S)-benzyl-3-hydroxypropyl)carbamic acid tert-butyl ester (VIII), with sodium azide and PPh3 gives the corresponding 3-azido derivative (IX), which is deprotected to afford 3-azido-2(S)-benzylpropylamine (X). The condensation of (X) with the intermediate bromopyrazinone (VII) by means of TEA in hot ethanol provides the secondary amine (XI), which is chlorinated with NCS in hot dichloroethane to give the chloropyrazinone (XII). The reduction of the azido group of (XII) by means of SnCl2 in methanol/THF yields the primary amine (XIII), which is condensed with the Boc protected 2-(5-bromopentyloxy)-5-chlorobenzylamine (XIV) by means of triethylamine in DMF to afford the linear precursor (XV). The deprotection of the NH2 group of (XV) by means of HCl provides the benzylamine derivative (XVI), which is treated with LiOH in THF to furnish the aminoacid precursor (XVII). Finally this compound is cyclized by means of EDC and HOAt to obtain the target macrolactam (1, 2).

参考文献中间体

合成目标

【1】 Nantermet, P.G.; Selnick, H.G.; Potent thrombin inhibitors via a 20-membered ring olefin metathesis macrocyclization. Tetrahedron Lett 2003, 44, 11, 2401.
【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)	63820	propyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate	C₉H₁₁BrN₂O₃	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)	63853	propyl 2-[3-{[(1S)-2-azido-1-benzylethyl]amino}-2-oxo-1(2H)-pyrazinyl]acetate	C₁₈H₂₂N₆O₃	详情	详情
(XII)	63854	propyl 2-[3-{[(1S)-2-azido-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₁₈H₂₁ClN₆O₃	详情	详情
(XIII)	63855	propyl 2-[3-{[(1S)-2-amino-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₁₈H₂₃ClN₄O₃	详情	详情
(XIV)	63856	tert-butyl 2-[(5-bromopentyl)oxy]-5-chlorobenzylcarbamate	C₁₇H₂₅BrClNO₃	详情	详情
(XV)	63857	ethyl 2-[3-[((1S)-1-benzyl-2-{[4-(2-{[(tert-butoxycarbonyl)amino]methyl}-4-chlorophenoxy)butyl]amino}ethyl)amino]-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₃₃H₄₃Cl₂N₅O₆	详情	详情
(XVI)	63858	methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-{(5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-7-({[(4-methylphenyl)sulfonyl]oxy}methyl)-3-[(4-nitrophenyl)sulfonyl]-1,2,3,4,5,6,7,8,9,10-decahydroazacycloundecino[5,4-b]indol-9-yl}-5-hydr; ethyl 2-[3-{[(1S)-2-({4-[2-(aminomethyl)-4-chlorophenoxy]butyl}amino)-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetate	C₅₉H₆₉N₅O₁₆S₂	详情	详情
(XVII)	63859	2-[3-{[(1S)-2-({4-[2-(aminomethyl)-4-chlorophenoxy]butyl}amino)-1-benzylethyl]amino}-6-chloro-2-oxo-1(2H)-pyrazinyl]acetic acid	C₂₆H₃₁Cl₂N₅O₄	详情	详情

Extended Information