3-chloro-5-isoxazolecarbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】25067

【品名】3-chloro-5-isoxazolecarbaldehyde

【CA登记号】

【分子式】C₄H₂ClNO₂

【分子量】131.51812

【元素组成】C 36.53% H 1.53% Cl 26.96% N 10.65% O 24.33%

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：(V)

The cephalosporin was synthesized following the reaction pathway depicted in Scheme 25490101a: Protected 2-(2-aminothiazol-4-yl)-2-(alkoxy)iminoacetic acid ((Ia-c) was reacted with p-methoxybenzyl 7-amino-3-chloromethyl-cephaslosporonate (II) by a conventional method (POCl3, pyr / CH2Cl2. -5 C) to give the acylated product (IIIa-c). Product (IIIa-c) was then coverted to a phosponium salt (Iva-c) (PPh3, NaI / acetone, r.t.), followed by the reaction (NaHCO3(2N) / CH2Cl2, 0 C - r.t.) with a substituted isoxazole aldehyde (V) to afford the protected final product (Via-c). The aldehyde (V) was prepared by the sequential reduction-oxidation of the 1,3-dipolar cycloaddition product of methyl propiolate and the corresponding aldoxime. Deprotection, sodium salt formation and purification by reverse phase column chromatography (LiChrosorb(R) RP-18, 25% aq. MeOH) followed by frezee drying gave the final product as an amorphous white solid.

参考文献中间体

合成目标

【1】 Choi, K.I.; Discovery of novel 3-isoxazolylvinylcephalosporins. Drugs Fut 1999, 24, 3, 287.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Ia)	25057	2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetic acid		C₄₃H₃₃N₃O₃S	详情	详情
(Ib)	25058	2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid	64485-90-1	C₂₅H₂₁N₃O₃S	详情	详情
(Ic)	25059	2-[(cyclopentyloxy)imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid		C₂₉H₂₇N₃O₃S	详情	详情
(IIIa)	25061	4-methoxybenzyl 3-(chloromethyl)-8-oxo-7-([2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₅₉H₄₈ClN₅O₆S₂	详情	详情
(IIIb)	25062	4-methoxybenzyl 3-(chloromethyl)-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₁H₃₆ClN₅O₆S₂	详情	详情
(IIIc)	25063	4-methoxybenzyl 3-(chloromethyl)-7-([2-[(cyclopentyloxy)imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₅H₄₂ClN₅O₆S₂	详情	详情
(IVa)	25064	[[2-[[(4-methoxybenzyl)oxy]carbonyl]-8-oxo-7-([2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl](triphenyl)phosphonium iodide		C₇₇H₆₃IN₅O₆PS₂	详情	详情
(IVb)	25065	[[2-[[(4-methoxybenzyl)oxy]carbonyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl](triphenyl)phosphonium iodide		C₅₉H₅₁IN₅O₆PS₂	详情	详情
(IVc)	25066	[(7-([2-[(cyclopentyloxy)imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-2-[[(4-methoxybenzyl)oxy]carbonyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl](triphenyl)phosphonium iodide		C₆₃H₅₇IN₅O₆PS₂	详情	详情
(VIa)	25068	4-methoxybenzyl 3-[(E)-2-(3-chloro-5-isoxazolyl)ethenyl]-8-oxo-7-([2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-[(trityloxy)imino]acetyl]amino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₆₃H₄₉ClN₆O₇S₂	详情	详情
(VIb)	25069	4-methoxybenzyl 3-[(E)-2-(3-chloro-5-isoxazolyl)ethenyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₅H₃₇ClN₆O₇S₂	详情	详情
(VIc)	25070	4-methoxybenzyl 3-[(E)-2-(3-chloro-5-isoxazolyl)ethenyl]-7-([2-[(cyclopentyloxy)imino]-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₉H₄₃ClN₆O₇S₂	详情	详情
(II)	25060	4-methoxybenzyl 3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₁₆H₁₆ClNO₄S	详情	详情
(V)	25067	3-chloro-5-isoxazolecarbaldehyde		C₄H₂ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Trityl protected 2-(2-aminothiazol-4-yl)-2-(methoxy)iminoacetic acid (I) was coupled to 7-amino-3-(chloromethyl)cephalosporanic acid p-methoxybenzyl ester (II) using POCl3 and pyridine to give amide (III). This was converted to phosphonium salt (IV) upon treatment with triphenylphosphine and NaI. Subsequent Wittig reaction of (IV) with 3-chloroisoxazole-5-carbaldehyde (V) produced the corresponding vinyl isoxazole as a mixture of geometrical isomers, from which the major trans isomer (VI) was separated by flash column chromatography. Finally, deprotection of both trityl and p-methoxybenzyl groups of (VI) by means of trifluoroacetic acid afforded the title compound, which was isolated as the sodium salt.

参考文献中间体

合成目标

【1】 Cho, Y.S.; Pae, A.N.; Cha, J.H.; Choi, K.I.; Chang, M.H.; Koh, H.Y.; Studies on novel 3-isoxazolylvinylcephalosporins: I. Synthesis and biological activity of 7-[2-(2-aminothiazol-4-yl)-2-(alkoxy)iminoacetamido] derivatives. J Antibiot 1998, 51, 12, 1117.

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)	25058	2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid	64485-90-1	C₂₅H₂₁N₃O₃S	详情	详情
(II)	26869	4-methoxybenzyl 7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₁₆H₁₇ClN₂O₄S	详情	详情
(III)	25062	4-methoxybenzyl 3-(chloromethyl)-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₁H₃₆ClN₅O₆S₂	详情	详情
(IV)	25065	[[2-[[(4-methoxybenzyl)oxy]carbonyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl](triphenyl)phosphonium iodide		C₅₉H₅₁IN₅O₆PS₂	详情	详情
(V)	25067	3-chloro-5-isoxazolecarbaldehyde		C₄H₂ClNO₂	详情	详情
(VI)	26870	4-methoxybenzyl 3-[(E)-2-(3-chloro-5-isoxazolyl)ethenyl]-7-([2-(methoxyimino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₄₅H₃₇ClN₆O₇S₂	详情	详情

Extended Information