Hydroxylamine -Drug Synthesis Database

【结构式】

【分子编号】32201

【品名】Hydroxylamine

【CA登记号】7803-49-8

【分子式】H₃NO

【分子量】33.02996

【元素组成】H 9.15% N 42.41% O 48.44%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(V)

Compound can be prepared in two different ways: 1) The cyclization of ethyl 2-[4-(chloroacetyl)phenyl]propionate (I) with 2-aminopyridine (II) in refluxing ethanol gives ethyl 2-[4-(imidazo[1,2-a]pyridin-2-yl)phenyl]propionate (III), which is then hydrolyzed with NaOH in refluxing ethanol water. 2) By cyclization of a mixture of pyridine (IV), hydroxylamine (V) and 2-[4-(chloroacetyl)phenyl]propionic acid (VI) by heating at 80-100 C.

参考文献中间体

合成目标

【1】 Muro, T.; Ogawa K.; JP 7703954 .
【2】 Nakanishi, M.; et al.; US 3978071 .
【3】 Hillier, K.; Y-9213. Drugs Fut 1979, 4, 5, 373.

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)	39470	ethyl 2-[4-(2-chloroacetyl)phenyl]propanoate		C₁₃H₁₅ClO₃	详情	详情
(II)	11305	2-Pyridinamine; 2-Pyridinylamine; 2-Aminopyridine	504-29-0	C₅H₆N₂	详情	详情
(III)	39471	ethyl 2-(4-imidazo[1,2-a]pyridin-2-ylphenyl)propanoate		C₁₈H₁₈N₂O₂	详情	详情
(IV)	29669	Pyridine	110-86-1	C₅H₅N	详情	详情
(V)	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情
(VI)	39472	2-[4-(2-chloroacetyl)phenyl]propionic acid		C₁₁H₁₁ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reaction of 2',4'-dichloro-2-imidazol-1-yl-acetophenone (I) with hydroxylamine (II) in refluxing ethanol pyridine gives the corresponding oxime (III). which is condensed with 2,4-dichlorobenzyl chloride (IV) by means of NaH in hot DMF.

参考文献中间体

合成目标

【1】 Thiele, K.; Mixich, G.; Ein beitrag zur stereospezifischen Synthese von antimykotisch wirksamen imidazolyloximathern. Arzneim-Forsch Drug Res 1979, 29, 10, 1510-13.
【2】 Mixich, G.; et al. (Siegfried AG); Imidazolyl-oxime ethers having anti-mycotic and bactericidal activity. DE 2657578; FR 2336129; GB 1514870; JP 52102276; US 4124767 .
【3】 Serradell, M.N.; Blancafort, P.; Hillier, K.; Castaner, J.; Oxiconazole nitrate. Drugs Fut 1981, 6, 2, 99.

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)	32200	1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone	46503-52-0	C₁₁H₈Cl₂N₂O	详情	详情
(II)	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情
(III)	32202	1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone oxime		C₁₁H₉Cl₂N₃O	详情	详情
(IV)	18345	2,4-Dichlorobenzyl chloride; 2,4-Dichloro-1-(chloromethyl)benzene	94-99-5	C₇H₅Cl₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

1. A mixture of diacid dichloride (I), aniline (II), hydroxylamine (III) and KOH in 50% THF/water gives, after chromatographic purification, the title product with yields of 15-30%.

参考文献中间体

合成目标

【1】 Breslow, R.; Rifkind, R.A.; Jursic, B. (Columbia University; Sloan-Kettering Institute); Novel potent inducers of terminal differentiation and methods of use thereof. WO 9307148 .

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)	53942	Suberic acid dichloride; Suberoyl chloride; Suberoyl dichloride	10027-07-3	C₈H₁₂Cl₂O₂	详情	详情
(II)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(III)	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情

合成路线4

该中间体在本合成路线中的序号：

Friedel-Crafts condensation of 2,5-dichloro-2,5-dimethylhexane (I) with toluene (II) in the presence of AlCl3 or FeCl3 afforded the tetrahydronaphthalene (III). Subsequent acylation of (III) with monomethyl terephthalic acid chloride (IV) provided keto ester (V), which was hydrolyzed to keto acid (VI) with methanolic KOH. Condensation of (VI) with hydroxylamine hydrochloride gave the corresponding oxime as a mixture of geometric isomers. The required Z isomer was then isolated by recrystallization from chloroform/hexane.

参考文献中间体

合成目标

【1】 Faul, M.M.; Ratz, A.M.; Sullivan, K.A.; Trankle, W.G.; Winneroski, L.L.; Synthesis of novel retinoid X receptor-selective retinoids. J Org Chem 2001, 66, 17, 5772.
【2】 Boehm, M.F.; Canan Koch, S.S.; Cesario, R.M.; Dardashti, L.J.; Nadzan, A.M.; Croston, G.E.; Heyman, R.A.; Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells. J Med Chem 1999, 42, 4, 742.
【3】 Zhang, L.; Boehm, M.F.; Badea, B.A.; White, S.K.; Mais, D.E.; Berger, E.; Suto, C.M.; Goldman, M.E..; Heyman, R.A.; Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem 1994, 37, 18, 2930.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情
(I)	35216	2,5-dichloro-2,5-dimethylhexane		C₈H₁₆Cl₂	详情	详情
(II)	12890	Toluene	108-88-3	C₇H₈	详情	详情
(III)	35217	1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene		C₁₅H₂₂	详情	详情
(IV)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(V)	35218	methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate		C₂₄H₂₈O₃	详情	详情
(VI)	35219	4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoic acid		C₂₃H₂₆O₃	详情	详情

合成路线5

该中间体在本合成路线中的序号：

Treatment of 2,2'-dimethylbenzophenone (I) with hydroxylamine afforded oxime (II), which was reduced to the benzhydryl amine (III) with sodium metal in liquid ammonia. Condensation of (III) with bromoacetyl bromide (IV) then produced the target amide (V).

参考文献中间体

合成目标

【1】 Chiou, W.J.; Liu, G.; Kozmina, N.S.; Opgenorth, T.J.; Winn, M.; Dixon, D.B.; Nguyen, B.; von geldern, T.W.; Marsh, K.C.; Design, synthesis, and activity of a series of pyrrolidine-3-carboxylic acid-based, highly specific, orally active ETB antagonists containing a diphenylmethylamine acetamide side chain. J Med Chem 1999, 42, 18, 3679.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情
(I)	35192	bis(2-methylphenyl)methanone		C₁₅H₁₄O	详情	详情
(II)	35193	bis(2-methylphenyl)methanone oxime		C₁₅H₁₅NO	详情	详情
(III)	35194	bis(2-methylphenyl)methanamine; bis(2-methylphenyl)methylamine		C₁₅H₁₇N	详情	详情
(IV)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(V)	35195	N-[bis(2-methylphenyl)methyl]-2-bromoacetamide		C₁₇H₁₈BrNO	详情	详情

Extended Information