2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride -Drug Synthesis Database

【结构式】

【分子编号】24316

【品名】2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride

【CA登记号】

【分子式】C₆H₆ClN₃O₂S

【分子量】219.65136

【元素组成】C 32.81% H 2.75% Cl 16.14% N 19.13% O 14.57% S 14.6%

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：(V)

The condensation of 3-(tert butoxycarbonyl amino)-1-hydroxy-4-methylazetidin-2-one (I) with chloroacetic acid (II) by means of K2CO3 gives 2-(3-(tert butoxycarbonylamino)-4-methyl-2-oxoazetidin-1-yloxy]acetic acid (III), which is deprotected with trifluoroacetic acid yielding 2-(3-amino 4-methyl-2-oxoazetidin-1-yloxy)acetic acid (IV). Finally, this compound is condensed with 2-(2-amino-thiazol-4-yl)-2-(methoxyimino)acetyl chloride (V) by means of Na2CO3.

参考文献中间体

合成目标

【1】 Breuer, H.; et al.; [(2-Oxo-1-azetidinyl)oxy]acetic acids: A new class of synthetic monobactams. J Antibiot 1985, 38, 6, 813.
【2】 Miller, M.J.; Woulfe, S.R.; Synthesis and biological activity of substituted [(3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids. A new class of heteroatom-activated beta-lactam antibiotics. J Med Chem 1985, 28, 10, 1447.
【3】 Breuer, H.; Straub, H.; Treuner, U.D. (Von Heyden); beta-Lactam derivs.. DE 3328047; GB 2125794 .
【4】 Castaner, J.; Prous, J.; Oximonam sodium. Drugs Fut 1986, 11, 9, 759.

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)	24312	butyl (2S,3S)-1-hydroxy-2-methyl-4-oxoazetidinylcarbamate		C₉H₁₆N₂O₄	详情	详情
(II)	11847	2-Chloroacetic acid; Chloroacetic Acid	79-11-8	C₂H₃ClO₂	详情	详情
(III)	24314	2-([(2S,3S)-3-[(butoxycarbonyl)amino]-2-methyl-4-oxoazetidinyl]oxy)acetic acid		C₁₁H₁₈N₂O₆	详情	详情
(IV)	24315	2-[[(2S,3S)-3-amino-2-methyl-4-oxoazetidinyl]oxy]acetic acid		C₆H₁₀N₂O₄	详情	详情
(V)	24316	2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride		C₆H₆ClN₃O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The reaction of N-(tert-butoxycarbonyl)-L-serine methyl ester (I) with hydrazine gives the corresponding hydrazide (II), which is acylated with trifluorothioacetic acid S-ethyl ester (III), yielding the diacylated hydrazine (IV). The cyclization of (IV) by means of DEAD and PPh3 affords the pyrazolidinone (V), which is deacylated with NaOH to furnish 4(S)-(tert-butoxycarbonyl)pyrazolidin-3-one (VI). The condensation of (VI) with vinylphosphonate (VII) gives the adduct (VIII), which is cyclized with the oxalyl monoester chloride (IX) by means of DIEA, yielding the pyrazolopyrazole (X). Finally, this compound is deprotected in acid medium and acylated with thiazole derivative (XI) by means of a Pd(0) catalyst to furnish the target compound.

参考文献中间体

合成目标

【1】 Ternansky, R.J.; Draheim, S.E.; The synthesis of bicyclic pyrazolidinone antibacterial agents. 30th Nat Org Symp (Vancouver) 1987.
【2】 Jungheim, L.N.; Holmes, R.E. (Eli Lilly and Company); Substd. diazolidinones. US 4826993 .
【3】 Jungheim, L.N.; Ternansky, R.J.; Holmes, R.E.; BICYCLIC PYRAZOLIDINONE ANTIBACTERIAL AGENTS. Drugs Fut 1990, 15, 2, 149.

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)	43221	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropanoate	2766-43-0	C₉H₁₇NO₅	详情	详情
(II)	43222	tert-butyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate		C₈H₁₇N₃O₄	详情	详情
(III)	43223	S-ethyl 2,2,2-trifluoroethanethioate	383-64-2	C₄H₅F₃OS	详情	详情
(IV)	43224	tert-butyl (1S)-1-(hydroxymethyl)-2-oxo-2-[2-(2,2,2-trifluoroacetyl)hydrazino]ethylcarbamate		C₁₀H₁₆F₃N₃O₅	详情	详情
(V)	43225	tert-butyl (4S)-3-oxo-1-(2,2,2-trifluoroacetyl)pyrazolidinylcarbamate		C₁₀H₁₄F₃N₃O₄	详情	详情
(VI)	43226	tert-butyl (4S)-3-oxopyrazolidinylcarbamate		C₈H₁₅N₃O₃	详情	详情
(VII)	43227	diethyl 1-cyanovinylphosphonate		C₇H₁₂NO₃P	详情	详情
(VIII)	43228	diethyl 2-[(4S)-4-[(tert-butoxycarbonyl)amino]-3-oxopyrazolidinyl]-1-cyanoethylphosphonate		C₁₅H₂₇N₄O₆P	详情	详情
(IX)	15585	allyl 2-chloro-2-oxoacetate		C₅H₅ClO₃	详情	详情
(X)	43229	allyl (6S)-6-[(tert-butoxycarbonyl)amino]-2-cyano-5-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-3-carboxylate		C₁₆H₂₀N₄O₅	详情	详情
(XI)	24316	2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride		C₆H₆ClN₃O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

参考文献中间体

合成目标

【1】 Ternansky, R.J.; Draheim, S.E.; The synthesis of bicyclic pyrazolidinone antibacterial agents. 30th Nat Org Symp (Vancouver) 1987.
【2】 Jungheim, L.N.; Holmes, R.E. (Eli Lilly and Company); Substd. diazolidinones. US 4826993 .
【3】 Jungheim, L.N.; Ternansky, R.J.; Holmes, R.E.; BICYCLIC PYRAZOLIDINONE ANTIBACTERIAL AGENTS. Drugs Fut 1990, 15, 2, 149.

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)	43221	methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropanoate	2766-43-0	C₉H₁₇NO₅	详情	详情
(II)	43222	tert-butyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate		C₈H₁₇N₃O₄	详情	详情
(III)	43223	S-ethyl 2,2,2-trifluoroethanethioate	383-64-2	C₄H₅F₃OS	详情	详情
(IV)	43224	tert-butyl (1S)-1-(hydroxymethyl)-2-oxo-2-[2-(2,2,2-trifluoroacetyl)hydrazino]ethylcarbamate		C₁₀H₁₆F₃N₃O₅	详情	详情
(V)	43225	tert-butyl (4S)-3-oxo-1-(2,2,2-trifluoroacetyl)pyrazolidinylcarbamate		C₁₀H₁₄F₃N₃O₄	详情	详情
(VI)	43226	tert-butyl (4S)-3-oxopyrazolidinylcarbamate		C₈H₁₅N₃O₃	详情	详情
(VII)	43230	diethyl 1-(methylsulfonyl)vinylphosphonate		C₇H₁₅O₅PS	详情	详情
(VIII)	43231	diethyl 2-[(4S)-4-[(tert-butoxycarbonyl)amino]-3-oxopyrazolidinyl]-1-(methylsulfonyl)ethylphosphonate		C₁₅H₃₀N₃O₈PS	详情	详情
(IX)	15585	allyl 2-chloro-2-oxoacetate		C₅H₅ClO₃	详情	详情
(X)	43232	allyl (6S)-6-[(tert-butoxycarbonyl)amino]-2-(methylsulfonyl)-5-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-3-carboxylate		C₁₆H₂₃N₃O₇S	详情	详情
(XI)	24316	2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl chloride		C₆H₆ClN₃O₂S	详情	详情

Extended Information