N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】61916

【品名】N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

【CA登记号】

【分子式】C₁₇H₁₈N₄O₃S

【分子量】358.42108

【元素组成】C 56.97% H 5.06% N 15.63% O 13.39% S 8.95%

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：(I)

The reaction of 3(R)-(tert-butoxycarbonylamino)-5-hexenoic acid (I) first with KI and I2, and then with NaN3 gives 6-azido-3(R)-(tert-butoxycarbonylamino)hexano-5-lactone (II), which is hydrolyzed with LiOH and protected with Tbdms-Cl to yield 6-azido-3(R)-(tert-butoxycarbonylamino)-5-(tert-butyldimethylsilyloxy)hexanoic acid (III). The reaction of acid (III) with pentafluorophenyl trifluoroacetate affords the corresponding activated ester as a mixture of diastereomers (IV) + (V). After separation, the desired diastereomer (IV) is condensed with 2-(1-methylhydrazino)acetic acid tert-butyl ester (VI) to provide the corresponding hydrazide (VII), which is reduced at the azido group by means of PPh3 in THF/water to give the amino compound (VIII). The condensation of (VIII) with 2-nitrophenylsulfonyl chloride (IX) by means of collidine in dichloromethane yields the sulfonamide (X), which is methylated with MeI and Cs2CO3 in DMF to afford the N-methylsulfonamide (XI). Finally, this compound is deprotected by reaction first with PhSH and K2CO3 and then with 4M HCl to provide the target hydrazide.

参考文献中间体

合成目标

【1】 Raju, B.; Mortell, K.; O'Dowd, H.; et al.; N- and C-terminal modifications of negamycin. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1685.

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)	61916	N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide		C₁₇H₁₈N₄O₃S	详情	详情
(II)	61923	tert-butyl (4R)-2-(azidomethyl)-6-oxotetrahydro-2H-pyran-4-ylcarbamate		C₁₁H₁₈N₄O₄	详情	详情
(III)	61924	(3R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoic acid		C₁₇H₃₄N₄O₅Si	详情	详情
(IV)	61926	2,3,4,5,6-pentafluorophenyl (3R,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoate		C₂₃H₃₃F₅N₄O₅Si	详情	详情
(V)	61925	2,3,4,5,6-pentafluorophenyl (3R,5S)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoate		C₂₃H₃₃F₅N₄O₅Si	详情	详情
(VI)	61909	tert-butyl 2-(1-methylhydrazino)acetate		C₇H₁₆N₂O₂	详情	详情
(VII)	61927	tert-butyl 2-[2-((3R,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoyl)-1-methylhydrazino]acetate		C₂₄H₄₈N₆O₆Si	详情	详情
(VIII)	61928	tert-butyl 2-[2-((3R,5R)-6-amino-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}hexanoyl)-1-methylhydrazino]acetate		C₂₄H₅₀N₄O₆Si	详情	详情
(IX)	32624	2-Nitrobenzenesulfonyl chloride	1694-92-4	C₆H₄ClNO₄S	详情	详情
(X)	61929	tert-butyl 2-[2-((3R,5R)-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(2-nitrophenyl)sulfonyl]amino}hexanoyl)-1-methylhydrazino]acetate		C₃₀H₅₃N₅O₁₀SSi	详情	详情
(XI)	61930	tert-butyl 2-[2-((3R,5R)-3-[(tert-butoxycarbonyl)amino]-5-{[tert-butyl(dimethyl)silyl]oxy}-6-{methyl[(2-nitrophenyl)sulfonyl]amino}hexanoyl)-1-methylhydrazino]acetate		C₃₁H₅₅N₅O₁₀SSi	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 cyclization of 4-(benzyloxycarbonylamino)acetophenone (I) with glyoxylic acid (II) and hydrazine (III) in hot acetic acid gives the pyridazinone (IV), which is treated first with Lawesson's reagent in hot dioxane and then with MeI and TEA in DMF to yield the methylsulfanyl pyridazine (V). The cyclization of (V) with acetamide (VI) by means of t-BuOLi in methanol/DMF affords the oxazolidinone (VII), which is finally treated with Lawesson's reagent in hot dioxane to provide the target thioacetamide.

参考文献中间体

合成目标

【1】 Luehr, G.W.; Wang, S.; Hackbarth, C.J.; Gomez, M.; Trias, J.; Patel, D.V.; Gordeev, M.F.; Novel antimicrobial pyridazine phenyloxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1320.

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)	61912	benzyl 4-acetylphenylcarbamate		C₁₆H₁₅NO₃	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	27344	hydrazine	302-01-2	H₄N₂	详情	详情
(IV)	61913	benzyl 4-(6-oxo-1,6-dihydro-3-pyridazinyl)phenylcarbamate		C₁₈H₁₅N₃O₃	详情	详情
(V)	61914	benzyl 4-[6-(methylsulfanyl)-3-pyridazinyl]phenylcarbamate		C₁₉H₁₇N₃O₂S	详情	详情
(VI)	61915	(1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate		C₇H₁₂ClNO₃	详情	详情
(VII)	61916	N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide		C₁₇H₁₈N₄O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

参考文献中间体

合成目标

【1】 Luehr, G.W.; Wang, S.; Hackbarth, C.J.; Gomez, M.; Trias, J.; Patel, D.V.; Gordeev, M.F.; Novel antimicrobial pyridazine phenyloxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1320.

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)	61912	benzyl 4-acetylphenylcarbamate		C₁₆H₁₅NO₃	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	27344	hydrazine	302-01-2	H₄N₂	详情	详情
(IV)	61913	benzyl 4-(6-oxo-1,6-dihydro-3-pyridazinyl)phenylcarbamate		C₁₈H₁₅N₃O₃	详情	详情
(V)	61914	benzyl 4-[6-(methylsulfanyl)-3-pyridazinyl]phenylcarbamate		C₁₉H₁₇N₃O₂S	详情	详情
(VI)	61915	(1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate		C₇H₁₂ClNO₃	详情	详情
(VII)	61916	N-[((5S)-3-{4-[6-(methylsulfanyl)-3-pyridazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide		C₁₇H₁₈N₄O₃S	详情	详情

Extended Information