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【结 构 式】

【药物名称】PD-0199646

【化学名称】6-[3(S)-Aminopyrrolidin-1-yl]-8-bromo-5-fluoro-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione

【CA登记号】

【 分 子 式 】C16H13BrFN3O3

【 分 子 量 】394.20271

【开发单位】Naeja (Originator), Pfizer (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, DNA Gyrase Inhibitors

合成路线1

Diazotation of 3-amino-6-nitro-1,8-naphthalic anhydride (I) in the presence of pyridine hydrofluoride afforded the fluoro derivative (II). This was brominated to (III) using Br2 and Ag2SO4 and its nitro group was subsequently reduced to amine (IV) with SnCl2. Sandmeyer reaction of amine (IV) in the presence of CuBr furnished the dibromo anhydride (V), which was treated with O-tert-butylhydroxylamine, yielding the N-tert-butoxy imide (VI). Regioselective displacement of one bromide group of (VI) with (S)-3-(Boc-amino)pyrrolidine (VII) gave rise to the protected pyrrolidinyl derivative (VIII). Finally, the tert-butyl protecting groups of (VIII) were removed by acidic treatment to produce the title compound.

1 Stier, M.A.; et al.; The synthesis and SAR of a series of 2-hydroxyisoquinolones: New antibacterial gyrase inhibitors. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1503.
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) 46342 5-amino-8-nitro-1H,3H-benzo[de]isochromene-1,3-dione C12H6N2O5 详情 详情
(II) 46343 5-fluoro-8-nitro-1H,3H-benzo[de]isochromene-1,3-dione C12H4FNO5 详情 详情
(III) 46344 6-bromo-5-fluoro-8-nitro-1H,3H-benzo[de]isochromene-1,3-dione C12H3BrFNO5 详情 详情
(IV) 46345 8-amino-6-bromo-5-fluoro-1H,3H-benzo[de]isochromene-1,3-dione C12H5BrFNO3 详情 详情
(V) 46346 6,8-dibromo-5-fluoro-1H,3H-benzo[de]isochromene-1,3-dione C12H3Br2FO3 详情 详情
(VI) 46347 6,8-dibromo-2-(tert-butoxy)-5-fluoro-1H-benzo[de]isoquinoline-1,3(2H)-dione C16H12Br2FNO3 详情 详情
(VII) 11685 tert-butyl N-[(3S)tetrahydro-1H-pyrrol-3-yl]carbamate C9H18N2O2 详情 详情
(VIII) 46348 tert-butyl (3S)-1-[8-bromo-2-(tert-butoxy)-5-fluoro-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl]pyrrolidinylcarbamate C25H29BrFN3O5 详情 详情
Extended Information