4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenylamine; 4-([[tert-butyl(dimethyl)silyl]oxy]methyl)aniline -Drug Synthesis Database

【结构式】

【分子编号】33423

【品名】4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenylamine; 4-([[tert-butyl(dimethyl)silyl]oxy]methyl)aniline

【CA登记号】

【分子式】C₁₃H₂₃NOSi

【分子量】237.41726

【元素组成】C 65.77% H 9.76% N 5.9% O 6.74% Si 11.83%

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：(I)

The condensation of 4-(tert-butyldimethylsilyloxymethyl)aniline (I) with 2-(acetoxy)benzoyl chloride (II) by means of TEA in dichloromethane gives the corresponding amide (III), which is oxidized with DMP in dichloromethane to yield the benzoquinone (IV). The reaction of (IV) with H2O2 and K2CO3 affords the epoxide (V), which is finally desilylated with HF and pyridine in THF to provide the target compound.

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; New synthetic technology for the construction of N-containing quinones and derivatives thereof: Total synthesis of epoxyquinomycin B. Angew Chem. Int Ed Engl 2001, 40, 1, 207.

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)	33423	4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenylamine; 4-([[tert-butyl(dimethyl)silyl]oxy]methyl)aniline		C₁₃H₂₃NOSi	详情	详情
(II)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情
(III)	50221	2-[[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)anilino]carbonyl]phenyl acetate		C₂₂H₂₉NO₄Si	详情	详情
(IV)	50222	2-([[4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,6-dioxo-1,4-cyclohexadien-1-yl]amino]carbonyl)phenyl acetate		C₂₂H₂₇NO₆Si	详情	详情
(V)	50223	N-[6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2,5-dioxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2-hydroxybenzamide		C₂₀H₂₅NO₆Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Coupling of the carboxylic acid (III) with the O-protected 4-aminobenzylalcohol (IX) as above and subsequent deprotection of the tert-butyldimethylsilyl (TBDMS) group with 6N HCl in acetone gave the benzylalcohol (X), which was reacted with thionyl chloride in chloroform/cat. pyridine to provide the benzylchloride (XI). Treatment of (XI) with the tertiary amine (XII) in DMF yielded TAK-779.

参考文献中间体

合成目标

【1】 Shiraishi, M.; Seto, M.; Aramaki, Y.; et al.; TAK-779, a small molecule CCR5 antagonist: Design, synthesis, and in vitro activity of anilide derivatives. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F911.
【2】 Shiraishi, M.; Aramaki, Y.; Seto, M.; et al.; Discovery of small molecule CCR5 antagonists. 19th Symp Med Chem and 8th Annu Meet Div Med Chem Jpn (Nov 17-19, Tokyo) 1999, Abst 2P-06.
【3】 Aramaki, Y.; Seto, M.; Shiraishi, M.; et al.; Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety. J Med Chem 2000, 43, 10, 2049.
【4】 Kanzaki, N.; Shiraishi, M.; Fujino, M.; Nishimura, O.; Baba, M.; Lizawa, Y.; TAK-779. Drugs Fut 2000, 25, 3, 252.
【5】 Kitayoshi, T.; Aramaki, Y.; Oda, T.; Honda, S.; Shiraishi, M. (Takeda Chemical Industries, Ltd.); Anilide deriv., production and use thereof. JP 1999263764; WO 9932468 .
【6】 Kuroshima, K.; Kanzaki, N.; Nishimura, O.; Shiraishi, M.; Sawada, H.; Baba, M.; Aramaki, Y. (Takeda Chemical Industries, Ltd.); Pharmaceutical composition for antagonizing CCR5 comprising anilide derivative. JP 2000128782; JP 2000128842; US 6096780; WO 9932100 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(III)	31560	2-(4-methylphenyl)-6,7-dihydro-5H-benzo[a]cycloheptene-8-carboxylic acid	C₁₉H₁₈O₂	详情	详情
(IX)	33423	4-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenylamine; 4-([[tert-butyl(dimethyl)silyl]oxy]methyl)aniline	C₁₃H₂₃NOSi	详情	详情
(X)	33424	N-[4-(hydroxymethyl)phenyl]-2-(4-methylphenyl)-6,7-dihydro-5H-benzo[a]cycloheptene-8-carboxamide	C₂₆H₂₅NO₂	详情	详情
(XI)	33425	N-[4-(chloromethyl)phenyl]-2-(4-methylphenyl)-6,7-dihydro-5H-benzo[a]cycloheptene-8-carboxamide	C₂₆H₂₄ClNO	详情	详情
(XII)	33426	N,N-dimethyltetrahydro-2H-pyran-4-amine; N,N-dimethyl-N-tetrahydro-2H-pyran-4-ylamine	C₇H₁₅NO	详情	详情

Extended Information