1-(4-aminophenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】27847

【品名】1-(4-aminophenyl)-1-ethanone

【CA登记号】99-92-3

【分子式】C₈H₉NO

【分子量】135.1656

【元素组成】C 71.09% H 6.71% N 10.36% O 11.84%

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：(VI)

This compound has been obtained by two different ways: 1) The oxidation of 4'-amino-3'-chloroacetophenone (I) with NaNO2 and HCl in water gives 3'-chloro-4-nitroacetophenone (II), which is condensed with 2,4-difluorophenol (III) by means of K2CO3 in xylene yielding 3'-(2,4-difluorophenyl)-4'-nitroacetophenone (IV). The reduction of (IV) with Fe and NH4Cl in ethanol affords the corresponding 4'-amino compound (V), which is finally treated with methanesulfonyl chloride and pyridine. 2) The reaction of 4'-aminoacetophenone (VI) with methanesulfonyl chloride as before gives the corresponding sulfonamide (VII), which is brominated with Br2 in acetic acid yielding N-(4-acetyl-3-bromophenyl)methanesulfonamide (VIII). Finally, this compound is condensed with 2,4-difluorophenol (III) by means of K2CO3 and CuCl as before.

参考文献中间体

合成目标

【1】 Zanka, A.; et al.; Process development of a novel anti-inflammatory agent. The regiospecific bromination of 4'-acetylmethanesulfonanilide. Org Process Res Dev 1998, 2, 2, 71.
【2】 Tsuji, K.; et al.; Studies on antiinflammatory agents. I. Synthesis and pharmacological properties of 2'-phenoxymethanesulfonanilide derivatives. Chem Pharm Bull 1992, 40, 9, 2399.

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)	33161	1-(4-amino-3-chlorophenyl)-1-ethanone		C₈H₈ClNO	详情	详情
(II)	33162	1-(3-chloro-4-nitrophenyl)-1-ethanone		C₈H₆ClNO₃	详情	详情
(III)	21486	2,4-difluorophenol	367-27-1	C₆H₄F₂O	详情	详情
(IV)	33163	1-[3-(2,4-difluorophenoxy)-4-nitrophenyl]-1-ethanone		C₁₄H₉F₂NO₄	详情	详情
(V)	33164	1-[4-amino-3-(2,4-difluorophenoxy)phenyl]-1-ethanone		C₁₄H₁₁F₂NO₂	详情	详情
(VI)	27847	1-(4-aminophenyl)-1-ethanone	99-92-3	C₈H₉NO	详情	详情
(VII)	33165	N-(4-acetylphenyl)methanesulfonamide		C₉H₁₁NO₃S	详情	详情
(VIII)	33166	N-(4-acetyl-2-bromophenyl)methanesulfonamide		C₉H₁₀BrNO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Preparation of the racemic arylpropionic acid (IX) has been reported through a number of different procedures. 4-Aminoacetophenone (XI) was diazotized to (XII) employing isoamyl nitrite and either acetic or fluoboric acid. Then, the Gomberg-Bachmann coupling of diazonium salt (XII) with 3-methylthiophene (XIII) furnished 4-(3-methyl-2-thienyl)acetophenone (XIV). Subsequent Darzen's condensation of acetophenone (XIV) with methyl chloroacetate (II) afforded the glycidic ester (XV), which was further hydrolyzed to acid (XVI), and then decarboxylated to aldehyde (XVII). Oxidation of (XVII) to the key carboxylic acid was performed by treatment with potassium permanganate

参考文献中间体

合成目标

【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 .
【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	10257	methyl 2-chloroacetate; methyl chloroacetate	96-34-4	C₃H₅ClO₂	详情	详情
(IX)	62687	2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid		C₁₄H₁₄O₂S	详情	详情
(XI)	27847	1-(4-aminophenyl)-1-ethanone	99-92-3	C₈H₉NO	详情	详情
(XII)	62688	4-acetylbenzenediazonium		C₈H₇N₂O	详情	详情
(XIII)	12442	3-Methylthiophene	616-44-4	C₅H₆S	详情	详情
(XIV)	62689	1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone		C₁₃H₁₂OS	详情	详情
(XV)	62690	methyl 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate		C₁₆H₁₆O₃S	详情	详情
(XVI)	62691	3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylic acid		C₁₅H₁₄O₃S	详情	详情
(XVII)	62692	2-[4-(3-methyl-2-thienyl)phenyl]propanal		C₁₄H₁₄OS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The N-alkylation of N-(tert-butoxycarbonyl)glycine (I) with benzyl bromide (II) by means of NaH in THF gives N-benzyl-N-(tert-butoxycarbonyl)glycine (III), which is condensed with 4-aminoacetophenone (IV) by means of isobutyl chloroformate and TEA in dichloromethane yielding the corresponding glycinamide (V). The cyclization of (V) with thiourea (VI) by means of I2 in refluxing isopropanol affords, after work up, the N-benzyl-glycinamide (VII), which is finally acylated with pyridine-4-carbonyl chloride by means of TEA and DMAP in dichloromethane.

参考文献中间体

合成目标

【1】 Hargrave, K.D.; Simoneau, B.; Faucher, A.-M.; Thavonekham, B.; Grygon, C.A.; Crute, J.J. (Boehringer Ingelheim (Canada) Ltd.; Boehringer Ingelheim Pharmaceuticals Inc.); Phenyl thiazole derivs. with anti-herpes virus properties. EP 0871619; JP 2000502702; US 6057451; WO 9724343 .

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)	18066	N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid	4530-20-5	C₇H₁₃NO₄	详情	详情
(II)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(III)	27846	2-[benzyl(tert-butoxycarbonyl)amino]acetic acid		C₁₄H₁₉NO₄	详情	详情
(IV)	27847	1-(4-aminophenyl)-1-ethanone	99-92-3	C₈H₉NO	详情	详情
(V)	27848	tert-butyl 2-(4-acetylanilino)-2-oxoethyl(benzyl)carbamate		C₂₂H₂₆N₂O₄	详情	详情
(VI)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VII)	27849	N-[4-(2-amino-1,3-thiazol-4-yl)phenyl]-2-(benzylamino)acetamide		C₁₈H₁₈N₄OS	详情	详情
(VIII)	27850	isonicotinoyl chloride	39178-35-3	C₆H₄ClNO	详情	详情

Extended Information