反应详情

温度

27 °C

Compound 13 (185 mg, 1 mmol) and 4-fluoro aniline (16, 147 mg, 1 mmol) was taken in ethylene glycol and refluxed at 150° C. for 5 h. Then the reaction mixture was cooled and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain Ethyl 2-(4-fluoroanilino) nicotinate (23) as pure product. Ethyl 2-(4-fluoroanilino) nicotinate (23, 260 mg, 1 mmol) were refluxed with 2N NaOH in ethanol for 2 h. The reaction mixture was cooled and left acidified with 2N HCl white solids obtained, filtered and washed with water to give pure compound of 2-(4-fluoroanilino)nicotic acid (30). To a stirred solution of 2-(4-fluorophenylamino) nicotinic acid (30, 232 mg 1 mmol) in dry DMF (10 mL) hydroxy benzotriazole HOBt (1.2 mmol) were added at 0° C. After 10 min 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) (1.2 mmol) was added and finally 2-amino 6-nitro benzothiazole 37 (137 mg, 0.7 mmol) were added, then the resulting mixture was stirred at room temperature (27° C.) for 8-10 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (6) was purified by column chromatography employing EtOAc/Hexane as an eluent.

1. temperatureThe reaction mixture was cooled
2. waitleft
3. customobtained
4. filtrationfiltered
5. washwashed with water
6. customto give pure compound of 2-(4-fluoroanilino)nicotic acid (30)
7. customthe reaction mixture was quenched with NaHCO3
8. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
9. dry with materialdried over anhydrous Na2SO4
10. customThe resulting product (6) was purified by column chromatography