2-fluoro-1,1'-biphenyl -Drug Synthesis Database

【结构式】

【分子编号】31388

【品名】2-fluoro-1,1'-biphenyl

【CA登记号】321-60-8

【分子式】C₁₂H₉F

【分子量】172.2018632

【元素组成】C 83.7% H 5.27% F 11.03%

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)

Friedel-Crafts condensation of 2-fluorobiphenyl (I) with glutaric anhydride (II) in the presence of AlCl3 gave ketoacid (III). Reduction of the ketonic group of (III) with triethylsilane in trifluoroacetic acid afforded biphenylpentanoic acid (IV), which was cyclized to the benzosuberone derivative (V) using polyphosphoric acid. Ketone reduction of (IV) by means of triethylsilane and trifluoroacetic acid provided the benzocycloheptene (VI), which was further oxidized to the isomeric ketone (VII) with chromic acid. Finally, condensation of (VII) with 5-fluoroisatin (VIII) in the presence of KOH yielded the target tetracyclic system.

参考文献中间体

合成目标

【1】 Suzuki, F.; Nakasato, Y.; Tsumuki, H.; Ohmori, K.; Nakajima, H.; Tamura, T.; Sato, S. (Kyowa Hakko Kogyo Co., Ltd.); Tetracyclic cpds.. US 5371225; WO 9322286 .

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)	31388	2-fluoro-1,1'-biphenyl	321-60-8	C₁₂H₉F	详情	详情
(II)	15512	Glutaric Anhydride; dihydro-2H-pyran-2,6(3H)-dione	108-55-4	C₅H₆O₃	详情	详情
(III)	31389	5-(2'-fluoro[1,1'-biphenyl]-4-yl)-5-oxopentanoic acid		C₁₇H₁₅FO₃	详情	详情
(IV)	31390	5-(2'-fluoro[1,1'-biphenyl]-4-yl)pentanoic acid		C₁₇H₁₇FO₂	详情	详情
(V)	31391	3-(2-fluorophenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one		C₁₇H₁₅FO	详情	详情
(VI)	31392	2-(2-fluorophenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene		C₁₇H₁₇F	详情	详情
(VII)	31393	2-(2-fluorophenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one		C₁₇H₁₅FO	详情	详情
(VIII)	21552	5-fluoro-1H-indole-2,3-dione	443-69-6	C₈H₄FNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Keto ester (III) was prepared by Friedel-Crafts acylation of 2-fluorobiphenyl (I) with methyl glutaryl chloride (II). Subsequent Pfitzinger condensation of (III) with 5-fluoroisatin (IV) furnished the quinoline derivative (V). Chlorination of diacid (V) with SOCl2, followed by treatment with methanol produced selectively the mono-ester (VI). The remaining carboxyl group of (VI) was activated with SOCl2 in the presence of DMF, and subsequently coupled with n-octyl amine to generate amide (VII). The methyl ester group of (VII) was then hydrolyzed to acid (VIII), which was further subjected to intramolecular ring closure upon heating with triflic acid to afford the tetracyclic system (IX). Keto group reduction in (IX) to give (X) was accomplished by a two-step procedure with NaBH4 and then with HI and Ac2O.

参考文献中间体

合成目标

【1】 Chujo, I.; et al.; Synthetic study on novel immunosuppressant KF20444. Bioorg Med Chem 2001, 9, 12, 3273.

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)	31388	2-fluoro-1,1'-biphenyl	321-60-8	C₁₂H₉F	详情	详情
(II)	20650	methyl 5-chloro-5-oxopentanoate; methyl-4-chloroformylbutyrate	1501-26-4	C₆H₉ClO₃	详情	详情
(III)	56572	methyl 5-(2'-fluoro[1,1'-biphenyl]-4-yl)-5-oxopentanoate		C₁₈H₁₇FO₃	详情	详情
(IV)	21552	5-fluoro-1H-indole-2,3-dione	443-69-6	C₈H₄FNO₂	详情	详情
(V)	56573	3-(2-carboxyethyl)-6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-quinolinecarboxylic acid		C₂₅H₁₇F₂NO₄	详情	详情
(VI)	56574	6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-(3-methoxy-3-oxopropyl)-4-quinolinecarboxylic acid		C₂₆H₁₉F₂NO₄	详情	详情
(VII)	56575	methyl 3-{6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-[(octylamino)carbonyl]-3-quinolinyl}propanoate		C₃₄H₃₆F₂N₂O₃	详情	详情
(VIII)	56576	3-{6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-[(octylamino)carbonyl]-3-quinolinyl}propanoic acid		C₃₃H₃₄F₂N₂O₃	详情	详情
(IX)	56577	10-fluoro-3-(2-fluorophenyl)-N-octyl-5-oxo-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carboxamide		C₃₃H₃₂F₂N₂O₂	详情	详情
(X)	56578	10-fluoro-3-(2-fluorophenyl)-N-octyl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carboxamide		C₃₃H₃₄F₂N₂O	详情	详情

Extended Information