ethyl 2-(1-phenylhydrazino)acetate -Drug Synthesis Database

【结构式】

【分子编号】25702

【品名】ethyl 2-(1-phenylhydrazino)acetate

【CA登记号】

【分子式】C₁₀H₁₄N₂O₂

【分子量】194.23344

【元素组成】C 61.84% H 7.27% N 14.42% O 16.47%

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 reaction of aniline (I) with ethyl bromoacetate (II) by means of triethylamine in benzene gives ethyl phenylaminoacetate (III), which is nitrosated with NaNO2 and HCl in water to yield ethyl N-nitrosophenylaminoacetate (IV). The reduction of (IV) with Zn in ethanol-water-acetic anhydride affords ethyl N1-phenylhydrazinoacetate (V), which is condensed with benzil (A) by means of HCl-sodium acetate in refluxing ethanol-water to yield ethyl alpha-benzoylbenzylidene-N1-phenylhydrazinoacetate (VI). The cyclization of (VI) by means of sodium ethoxide in refluxing ethanol gives 1,3,4-triphenylpyrazole-5-carboxylic acid (VII), which is reduced with LiAlH4 in ether-THF to produce 1,3,4-triphenyl-5-(hydroxymethyl)pyrazole (VIII). The reaction of (VIII) with SOCl2 in refluxing chloroform yields 1,3,4-triphenyl-5-(chloromethyl)pyrazole (IX), which by reaction with NaCN in hot DMSO is converted into 1,3,4-triphenylpyrazole-5-acetonitrile (X). Finally, this compound is hydrolyzed by means of NaOH in refluxing aqueous ethanol.

参考文献中间体

合成目标

【1】 Gueremy, C.; Renault, C.; US 3984431 .
【2】 Castaner, J.; Arrigoni, Martelli, E.; Isofezolac. Drugs Fut 1980, 5, 1, 21.

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)	39056	Dibenzoyl; benzil	134-81-6	C₁₄H₁₀O₂	详情	详情
(I)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	25701	ethyl 2-anilinoacetate	2216-92-4	C₁₀H₁₃NO₂	详情	详情
(IV)	39055			C₁₀H₁₂N₂O₃	详情	详情
(V)	25702	ethyl 2-(1-phenylhydrazino)acetate		C₁₀H₁₄N₂O₂	详情	详情
(VI)	39057	ethyl (Z)-4-oxo-3,4-diphenyl-2-(1-phenylhydrazino)-2-butenoate		C₂₄H₂₂N₂O₃	详情	详情
(VII)	39058	1,3,4-triphenyl-1H-pyrazole-5-carboxylic acid		C₂₂H₁₆N₂O₂	详情	详情
(VIII)	39059	(1,3,4-triphenyl-1H-pyrazol-5-yl)methanol		C₂₂H₁₈N₂O	详情	详情
(IX)	39060	5-(chloromethyl)-1,3,4-triphenyl-1H-pyrazole		C₂₂H₁₇ClN₂	详情	详情
(X)	39061	2-(1,3,4-triphenyl-1H-pyrazol-5-yl)acetonitrile		C₂₃H₁₇N₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Synthesis of [18F]FEtNTI: The intermediate 2-(N1-phenylhydrazino)acetic acid ethyl ester (II) has been obtained by two different ways: 1.- By nitrosation of N-phenylglycine ethyl ester (I) with NaNO2 followed by readuction with Zn/acetic acid (low yields). 2.- By condensation of phenylhydrazine (III) with ethyl bromoacetate (IV) by means of an excess of triethylamine. The cyclization of intermediate (II) with naltrexone (V) by mans of HCl in methanol gives the indolomorphinanylacetic ester (VI), which is benzyl protected at the OH group by means of benzyl bromide and K2CO3 in DMF yielding the benzyl ether (VII). The reduction of the ester group of (VII) with LiAlH4 in THF/toluene afords the indolomorphinanylethanol (VIII), which is treated with tosyl chloride and potassium trimethylsilanolate in toluene to provide the corresponding tosylate (IX). The reaction of (IX) with potassium [18F]fluoride, K2CO3 and Kryptpfix [2.2.2] in hot DMF gives the 18F labeled intermediate (X), which is finally debenzylated by hydrogenation with H2 over Pd/C in DMF/triethylamine.

参考文献中间体

合成目标

【1】 Mathews, W.B.; et al.; Synthesis of N1´-([F-18]fluoroethyl)naltrindole ([F-18]FEtNTI): A radioligand for positron emission tomographic studies of delta opioid receptors. J Label Compd Radiopharm 1999, 42, 1, 43.

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)	25701	ethyl 2-anilinoacetate	2216-92-4	C₁₀H₁₃NO₂	详情	详情
(II)	25702	ethyl 2-(1-phenylhydrazino)acetate		C₁₀H₁₄N₂O₂	详情	详情
(III)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情
(IV)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(V)	25079	(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one; Naltrexone	16590-41-3	C₂₀H₂₃NO₄	详情	详情
(VI)	25704	ethyl 2-[(1S,2S,13S,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-11-yl]acetate		C₃₁H₃₃NO₅	详情	详情
(VII)	25705	ethyl 2-[(1S,2S,13S,21R)-16-(benzyloxy)-22-(cyclopropylmethyl)-2-hydroxy-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-11-yl]acetate		C₃₈H₃₉NO₅	详情	详情
(VIII)	25706	(1S,2S,13S,21R)-16-(benzyloxy)-22-(cyclopropylmethyl)-11-(2-hydroxyethyl)-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-2-ol		C₃₆H₃₇NO₄	详情	详情
(IX)	25707	2-[(1S,2S,13S,21R)-16-(benzyloxy)-22-(cyclopropylmethyl)-2-hydroxy-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-11-yl]ethyl 4-methylbenzenesulfonate		C₄₃H₄₃NO₆S	详情	详情
(X)	25708	(1S,2S,13S,21R)-16-(benzyloxy)-22-(cyclopropylmethyl)-11-(2-fluoroethyl)-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-2-ol		C₃₆H₃₆FNO₃	详情	详情
(X)	45358	(1S,2S,13S,21R)-16-(benzyloxy)-22-(cyclopropylmethyl)-11-(2-fluoroethyl)-14-oxa-22-azaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-2-ol		C₃₆H₃₆FNO₃	详情	详情

Extended Information