2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】59365

【品名】2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid

【CA登记号】85-52-9

【分子式】C₁₄H₁₀O₃

【分子量】226.2316

【元素组成】C 74.33% H 4.46% O 21.22%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(I)

The reaction of 2-benzoylbenzoic acid (I) with SOCl2 in CHCl3, benzene or DMF gives the corresponding acyl chloride (II), which is condensed with ethanolamine (III) by means of TEA in CHCl3 to yield the amide (IV). The reduction of (IV) with LiAlH4 in THF affords the diol (V), which is cyclized by means of Ts-OH in refluxing benzene to provide 1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine (VI). Finally, this compound is methylated by means of dimethyl sulfate in refluxing benzene, or by means of formaldehyde in hot dioxane/water. Alternatively, the cyclization of N-[2-[1-[2-(chloromethyl)phenyl]-1-phenylmethoxy]ethyl]-N-methylamine (VII) by means of pyridine in refluxing acetonitrile gives also the target benzoxazocine.

参考文献中间体

合成目标

【1】 Lazaro Porta, A.; Process for the preparation of diphenylcarbinol derivs.. ES 8100663 .
【2】 Calatayud, J.; Luna, M.; Process for the preparation of 5-phenyl-1-methyl-1-aza-4-oxa-6,7-benzocyclooctane hydrochloride. ES 8605495 .
【3】 Colls Alsius, J.; Process for the preparation of of a heterocyclic tertiary amine. ES 8607261 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(IV)	59367	2-benzoyl-N-(2-hydroxyethyl)benzamide		C₁₆H₁₅NO₃	详情	详情
(V)	59368	2-({2-[hydroxy(phenyl)methyl]benzyl}amino)-1-ethanol		C₁₆H₁₉NO₂	详情	详情
(VI)	59369	1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine		C₁₆H₁₇NO	详情	详情
(VII)	59370	2-[[2-(chloromethyl)phenyl](phenyl)methoxy]-N-methyl-1-ethanamine; N-{2-[[2-(chloromethyl)phenyl](phenyl)methoxy]ethyl}-N-methylamine		C₁₇H₂₀ClNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 2-benzoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which is condensed with 2-(methylamino)acetic acid (III) in benzene to yield the N-(2-benzoylbenzoyl)-N-methylglycine (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords the diol (V), which is finally cyclized by means of PPA at 80 C to provide the target benzoxazocine.

参考文献中间体

合成目标

【1】 Galiano Ramos, J.A.; Verde Casanova, M.J.; Fernandez Torija, C. (Instituto de Investigacion y Desarrollo Quimico Biologico SA); Process for the preparation of 1-methyl-5-phenyl-aza-4-oxo-6,7-benzocyclooctane. ES 8104800 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	10429	N-Methylglycine; Sarcosine; 2-(Methylamino)acetic acid	107-97-1	C₃H₇NO₂	详情	详情
(IV)	59376	2-[(2-benzoylbenzoyl)(methyl)amino]acetic acid		C₁₇H₁₅NO₄	详情	详情
(V)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The reaction of 2-benzoylbenzoic acid (I) with PCl3 in dichloromethane gives the corresponding acyl chloride (II), which is condensed with N-methylethanolamine (III) by means of TEA In dichloroethane to yield the amide (IV). The reaction of (IV) with PCl3 in dichloroethane affords the 2-chloroethylamide (V), which is reduced with NaBH4 and A-OH in dichloromethane to provide the diol (VI). Finally, this compound is cyclized by means of aq. HBr in dichloroethane to give the target benzoxazocine.

参考文献中间体

合成目标

【1】 Watson, P.G.; Process for the preparation of 2-[N-(2-hydroxyethyl)-N-lower alkylaminomethyl]benzhydrols. US 4208349 .
【2】 Watson, P.G.; Process for the preparation of 2-[N-(2-hydroxyethyl)-N-lower alkylaminomethyl)benzhydrols. GB 1586578 .

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)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(II)	59366	2-benzoylbenzoyl chloride		C₁₄H₉ClO₂	详情	详情
(III)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(IV)	59374	2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide	24833-47-4	C₁₇H₁₇NO₃	详情	详情
(V)	59377	2-benzoyl-N-(2-chloroethyl)-N-methylbenzamide		C₁₇H₁₆ClNO₂	详情	详情
(VI)	59375	2-[{2-[hydroxy(phenyl)methyl]benzyl}(methyl)amino]-1-ethanol		C₁₇H₂₁NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

The title compound is prepared according to the Ugi reaction by combination of the four components: isocyanide (III), m-cyanobenzaldehyde (IV), 2-benzoylbenzoic acid (V), and histamine (VI) in refluxing MeOH

参考文献中间体

合成目标

【1】 Hirth, B.H.; Bernasconi, R.; Biemann, H.P.; et al.; Discovery of TNF-alpha induced apoptosis inhibitors with activity in a murine model of multiple sclerosis: Glycine diamides. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 272.
【2】 Hirth, B.H.; Sneddon, S.F.; Kane, J.L.; Vinick, F.; Qiao, S.; Nahill, S.R. (Genzyme Corp.); Modulators of TNF-alpha signaling. WO 0187849 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	60310			C₁₅H₁₃N	详情	详情
(IV)	13245	3-Formylbenzonitrile; 3-Cyanobenzaldehyde	24964-64-5	C₈H₅NO	详情	详情
(V)	59365	2-benzophenone carboxylic acid; 2-Benzoylbenzoic acid; 2-Carboxybenzophenone; Benzophenone-2-carboxylic acid; O-benzoylbenzoic acid	85-52-9	C₁₄H₁₀O₃	详情	详情
(VI)	60311	2-(1H-imidazol-5-yl)-1-ethanamine; 2-(1H-imidazol-5-yl)ethylamine		C₅H₉N₃	详情	详情

Extended Information