Phosphorus oxychloride → 5-(4-Bromo-2-fluoro-phenylamino)-8-fluoro-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester
反応式
[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH2:11][NH:12][CH:13]=O)=[N:6][C:5]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[F:23].P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([F:10])[C:7]2[N:6]([CH:13]=[N:12][CH:11]=2)[C:5]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[F:23])=[O:24]参加物
4
反応条件
- 温度
- 90 °C
実験手順
To a suspension of 2-(4-bromo-2-fluoro-phenylamino)-5-fluoro-6-formylaminomethyl-nicotinic acid methyl ester (2.49 g, 6.2 mmol) in toluene (60 mL) was added phosphorous oxychloride (0.65 mL, 7.0 mmol). The reaction mixture was heated to 90° C. and stirred for 1.5 hour before cooling to room temperature and concentrating in vacuo. The resultant residue was dissolved in ethyl acetate and washed with water followed by a saturated aqueous solution of sodium bicarbonate and then brine. The organic phase was isolated, dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ether in hexane) to afford the title compound as a yellow solid (692 mg, 29%). LCMS (method B): RT=3.97 min, [M+H]+=382/384.