6-fluoro-2-methyl-4H-3,1-benzoxazin-4-one -Drug Synthesis Database

【结构式】

【分子编号】38462

【品名】6-fluoro-2-methyl-4H-3,1-benzoxazin-4-one

【CA登记号】

【分子式】C₉H₆FNO₂

【分子量】179.1505832

【元素组成】C 60.34% H 3.38% F 10.6% N 7.82% O 17.86%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(II)

Hydrogenation of 2-nitro-5-fluorobenzoic acid (I), followed by in situ condensation with acetic anhydride produced benzoxazinone (II). Subsequent reaction of (III) with 2-chloroaniline (III) in refluxing AcOH furnished quinazolinone (IV). Treatment of (IV) with 2,6-pyridinedicarboxaldehyde (V) in the presence of ZnCl2 and Ac2O gave rise to the pyridinylvinyl derivative (VI). The title amine was finally obtained by reductive amination of aldehyde (VI) with diethylamine using NaBH(OAc)3). The two atropisomers were separated by means of preparative chiral HPLC.

参考文献中间体

合成目标

【1】 Ewing, F.E.; Welch, W.M.; Huang, J.; et al.; Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-ethyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. Bioorg Med Chem Lett 2001, 11, 2, 177.
【2】 Elliott, M.L.; Welch, W.M. Jr. (Pfizer Inc.); Novel 2,3 disubstd.-4(3H)-quinazolinones. EP 0901487; JP 1999514663; WO 9743276 .
【3】 Welch, W.M. Jr.; DeVries, K.M. (Pfizer Inc.); Atropisomers of 3-aryl-4(3H)-quinazolinones and their use as AMPA-receptor antagonists. EP 0968194; JP 2000509731; WO 9838173 .

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)	31962	2-Nitro-5-fluorobenzoic acid; 5-Fluoro-2-nitrobenzoic acid	320-98-9	C₇H₄FNO₄	详情	详情
(II)	38462	6-fluoro-2-methyl-4H-3,1-benzoxazin-4-one		C₉H₆FNO₂	详情	详情
(III)	35804	2-chloroaniline; 2-chlorophenylamine	95-51-2	C₆H₆ClN	详情	详情
(IV)	38463	3-(2-chlorophenyl)-6-fluoro-2-methyl-4(3H)-quinazolinone		C₁₅H₁₀ClFN₂O	详情	详情
(V)	38464	2,6-pyridinedicarbaldehyde	5431-44-7	C₇H₅NO₂	详情	详情
(VI)	38465	6-[(E)-2-[3-(2-chlorophenyl)-6-fluoro-4-oxo-3,4-dihydro-2-quinazolinyl]ethenyl]-2-pyridinecarbaldehyde		C₂₂H₁₃ClFN₃O₂	详情	详情

Extended Information