反应详情

温度

105 °C

In a round-bottomed flask, N-(5-fluoro-pyridin-2-ylmethyl)-oxalamic acid methyl ester (crude from Step 1) was dissolved in toluene (8 ml) and phosphorus oxychloride (1.5 ml, 16.1 mmol) was added. The reaction mixture was stirred at 105° C. in an oil bath overnight then cooled to 0° C. and carefully quenched with ice. Aqueous 25% ammonium hydroxide was added until pH=˜9. The mixture was diluted with water and extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-50% EtOAc) to give 230 mg (31%, 2 steps) of 6-fluoro-imidazo[1,5-a]pyridine-3-carboxylic acid methyl ester as a light brown solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 9.33 (dd, J=5.1, 1.3 Hz, 1H), 7.75 (s, 1H), 7.69 (dd, J=9.8, 5.3 Hz, 1H), 7.09 (ddd, J=9.7, 7.5, 2.1 Hz, 1H), 4.06 (s, 3H).

1. temperaturethen cooled to 0° C.
2. customcarefully quenched with ice
3. additionAqueous 25% ammonium hydroxide was added until pH=˜9
4. additionThe mixture was diluted with water
5. extractionextracted with dichloromethane (3×)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was absorbed on silica gel
10. customchromatographed with EtOAc/hexanes (gradient 0-50% EtOAc)