1-[2-(chlorooxy)-2-oxoethyl]benzene -Drug Synthesis Database

【结构式】

【分子编号】24261

【品名】1-[2-(chlorooxy)-2-oxoethyl]benzene

【CA登记号】

【分子式】C₈H₇ClO₂

【分子量】170.59508

【元素组成】C 56.33% H 4.14% Cl 20.78% O 18.76%

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：(II)

The acylation of valienamine (I) with benzyloxycarbonyl chloride (II) by means of NaHCO3 in ethyl acetate gives the corresponding N-benzyloxycarbonyl derivative (III), which by reaction with Br2 in water is converted to the cyclic carbamate (IV). Elimination of bromine from (IV) with NaBH4 in water affords the new cyclic carbamate (V), which by hydrolysis with Ba(OH)2 in refluxing water is converted to valiolamine (VI). Finally, this compound is reductocondensed with 1,3-dihydroxyacetone (VII) and sodium cyanoborohydride in DMF 2N HCl.

参考文献中间体

合成目标

【1】 Horii, S.; et al.; Synthesis and alpha-D-glucosidase inhibitory activity of N-substituted valiolamine derivatives as potential oral antidiabetic agents. J Med Chem 1986, 29, 6, 1038.
【2】 Horii, S.; Kameda, Y.; Fukase, H. (Takeda Chemical Industries, Ltd.); N-substituted pseudo-aminosugars, their production and use. EP 0056194; US 4701559; US 4777294; US 4803303 .
【3】 Prous, J.; Castaner, J.; AO-128. Drugs Fut 1986, 11, 9, 729.

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)	24260	(1S,2S,3R,6S)-4-(hydroxymethyl)-6-(methylamino)-4-cyclohexene-1,2,3-triol		C₈H₁₅NO₄	详情	详情
(II)	24261	1-[2-(chlorooxy)-2-oxoethyl]benzene		C₈H₇ClO₂	详情	详情
(III)	24262	(1S,2S,3R,6S)-4-(hydroxymethyl)-6-[methyl[(2-phenylacetyl)oxy]amino]-4-cyclohexene-1,2,3-triol		C₁₆H₂₁NO₆	详情	详情
(IV)	24263	(1S,5R,6S,7R,8S,9S)-9-bromo-6,7,8-trihydroxy-1-(hydroxymethyl)-4-methyl-2-oxa-4-azabicyclo[3.3.1]nonan-3-one		C₉H₁₄BrNO₆	详情	详情
(V)	24264	(1S,5S,6S,7R,8S)-6,7,8-trihydroxy-1-(hydroxymethyl)-4-methyl-2-oxa-4-azabicyclo[3.3.1]nonan-3-one		C₉H₁₅NO₆	详情	详情
(VI)	24265	(1S,2S,3R,4S,5S)-1-(hydroxymethyl)-5-(methylamino)-1,2,3,4-cyclohexanetetrol		C₈H₁₇NO₅	详情	详情
(VII)	14575	Dihydroxyacetone; 1,3-dihydroxyacetone	96-26-4	C₃H₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

By reaction of benzyl chloroformate (I) with epinine hydrobromide (II) in sodium tetraborate and 2N NaOH to give the compound (III), which is esterified with isobutanoyl chloride (A) in pyridine giving (IV), which is debenzylated with H2.

参考文献中间体

合成目标

【1】 Casagrande, C.; Ferrari, G. (Simes SpA); Epinine esters and pharmaceutical compositions thereof. DE 2734678; ES 461399; FR 2360558; GB 1551661; JP 53021130; US 4218470 .
【2】 Doherty, J.B.; Rupprecht, K.M.; Goulet, J.L.; Chen, M.-H.; Bao, J.; Liu, L.; Miao, S.; Hunt, J.A.; Hong, X.; Stelmach, J.E.; Ruzek, R.D.; Wisnoski, D.D.; Natarajan, S.R. (Merck & Co., Inc.); (Halo-benzo carbonyl)heterocyclic fused phenyl p38 kinase inhibiting agents. EP 1345603; WO 0258695 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情
(I)	24261	1-[2-(chlorooxy)-2-oxoethyl]benzene		C₈H₇ClO₂	详情	详情
(II)	32285	4-[2-(methylamino)ethyl]-1,2-benzenediol		C₉H₁₃NO₂	详情	详情
(III)	32286	benzyl 3,4-dihydroxyphenethyl(methyl)carbamate		C₁₇H₁₉NO₄	详情	详情
(IV)	32287	4-[2-[[(benzyloxy)carbonyl](methyl)amino]ethyl]-2-(isobutyryloxy)phenyl 2-methylpropanoate		C₂₅H₃₁NO₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(A)

The reaction of 1-amino-5-nitropentane (I) with benzyloxycarbonyl chloride (A) by means of NaOH in water gives 1-carbobenzoxyamino-5-nitropentane (II), which by reduction with Zn and ammonium chloride in ethanol - water yields 1-carbobenzoxyamino-5-hydroxylaminopentane (III). The reaction of (III) with succinic anhydride (B) by means of NaOH in pyridine water affords 1-carbobenzoxyamino-5-(N-succinylhydroxylamino)pentane (IV), which is cyclized with hot acetic anhydride giving 2-(5-carbobenzoxyaminopentyl)-3,6-dioxotetrahydro-1,2-oxazine (V). The reaction of (V) with the nitroamine (I) by means of sodium methoxide in methanol yields 1-carbobenzoxy-6-hydroxy-16-nitro-7,10-dioxo-6,11-diazahexadecane (VI), which is reduced with Zn and acetylated as before affording 1-carboxybenzoxyamino-6-hydroxy-16-(N-acetylhydroxylamino)-7,10-dioxo-6,11-diazahexadecane (VII).

参考文献中间体

合成目标

【1】 Prelog, V.; Walser, A.; 75. Stoffweschselprodukte con actinomyceten. Uber die synthese der ferrioxamine B und D1. Helv Chim Acta 1962, 45, 631-637.
【2】 Bickel, H.; et al.; 153. Stoffweschselprodukte von mikroorganismen. Zur henntnis von desferrioxamin B. Helv Chim Acta 1963, 46, 1385-89.
【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hopkins, S.J.; Liposome-Entrapped Desferrioxamine deferoxamine. Drugs Fut 1979, 4, 7, 500.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	11291	Dihydro-2,5-furandione; Succinic anhydride	108-30-5	C₄H₄O₃	详情	详情
(A)	24261	1-[2-(chlorooxy)-2-oxoethyl]benzene		C₈H₇ClO₂	详情	详情
(I)	33387	5-nitropentylamine; 5-nitro-1-pentanamine		C₅H₁₂N₂O₂	详情	详情
(II)	33388	benzyl 5-nitropentylcarbamate		C₁₃H₁₈N₂O₄	详情	详情
(III)	33389	benzyl 5-(hydroxyamino)pentylcarbamate		C₁₃H₂₀N₂O₃	详情	详情
(IV)	33390	4-[(5-[[(benzyloxy)carbonyl]amino]pentyl)(hydroxy)amino]-4-oxobutyric acid		C₁₇H₂₄N₂O₆	详情	详情
(V)	33391	benzyl 5-(3,6-dioxo-1,2-oxazinan-2-yl)pentylcarbamate		C₁₇H₂₂N₂O₅	详情	详情
(VI)	33392	benzyl 5-(hydroxy[4-[(5-nitropentyl)amino]-4-oxobutanoyl]amino)pentylcarbamate		C₂₂H₃₄N₄O₇	详情	详情
(VII)	33393	benzyl 5-[[4-([5-[acetyl(hydroxy)amino]pentyl]amino)-4-oxobutanoyl](hydroxy)amino]pentylcarbamate		C₂₄H₃₈N₄O₇	详情	详情

Extended Information