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【结 构 式】

【分子编号】56574

【品名】6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-(3-methoxy-3-oxopropyl)-4-quinolinecarboxylic acid

【CA登记号】

【 分 子 式 】C26H19F2NO4

【 分 子 量 】447.4380064

【元素组成】C 69.79% H 4.28% F 8.49% N 3.13% O 14.3%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VI)

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.

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

合成路线2

该中间体在本合成路线中的序号:(VI)

In a different strategy for protecting the quinoline carboxyl group, acid (VI) was reduced to alcohol (XI) via chlorination with SOCl2, followed by treatment with NaBH4. Alcohol (XI) was then converted to the alkyl chloride (XII) with SOCl2 in dichloroethane. Subsequent ester group hydrolysis in (XII) under acidic conditions furnished the carboxylic acid (XIII). The tetracyclic compound (XIV) was obtained by cyclization of acid (XIII) in hot triflic acid. Displacement of the chloride group of (XIV) with sodium acetate in HOAc yielded acetate ester (XV), which was subsequently hydrolyzed to alcohol (XVI). Oxidation of (XVI) with DMSO and Ac2O provided aldehyde (XVII).

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
(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
(XI) 56579 methyl 3-[6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-(hydroxymethyl)-3-quinolinyl]propanoate C26H21F2NO3 详情 详情
(XII) 56580 methyl 3-[4-(chloromethyl)-6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-quinolinyl]propanoate C26H20ClF2NO2 详情 详情
(XIII) 56581 3-[4-(chloromethyl)-6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-quinolinyl]propanoic acid C25H18ClF2NO2 详情 详情
(XIV) 56582 8-(chloromethyl)-10-fluoro-3-(2-fluorophenyl)-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinolin-5-one C25H16ClF2NO 详情 详情
(XV) 56583 [10-fluoro-3-(2-fluorophenyl)-5-oxo-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinolin-8-yl]methyl acetate C27H19F2NO3 详情 详情
(XVI) 56584 10-fluoro-3-(2-fluorophenyl)-8-(hydroxymethyl)-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinolin-5-one C25H17F2NO2 详情 详情
(XVII) 56585 10-fluoro-3-(2-fluorophenyl)-5-oxo-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carbaldehyde C25H15F2NO2 详情 详情
Extended Information