1. 3-Pyrrole carboxylic acid (500 mg, 4.5 mmol), dicyclohexylcarbodiimide (1.11 g, 5.4 mmol), 4-dimethylaminopyridine (DMAP) (54 mg, 0.45 mmol) and ethanol (3.2 mL, 54 mmol) were dissolved in tetrahydrofuran (THF) (15 mL).
2. The reaction mixture was heated at 60 °C for 10 h and then cooled to room temperature.
3. The reaction mixture was filtered to remove the precipitate and the filter cake was washed with ethyl acetate.
4. The filtrates were combined, concentrated under reduced pressure and then purified by silica gel column chromatography to afford ethyl 1H-pyrrole-3-carboxylate (500 mg, 81%) as a colorless oil.
5. A benzene (1 mL) solution of 2-chloronicotinoyl chloride (493 mg, 2.8 mmol) was added to a benzene (3 mL) solution of ethyl 1H-pyrrole-3-carboxylate (390 mg, 2.8 mmol).
6. Stannic chloride (IV) (0.5 mL) was added dropwise to the mixture under nitrogen protection and then stirred overnight at room temperature.
7. After completion of the reaction, the reaction mixture was treated with 2N HCl and extracted with ethyl acetate.
8. The organic phases were combined, dried and concentrated under reduced pressure to give ethyl 5-(2-chloropyridine-3-carbonyl)-1H-pyrrole-3-carboxylate (390 mg, 50%) as a white solid.
9. A solution of ethyl 5-(2-chloropyridine-3-carbonyl)-1H-pyrrole-3-carboxylate (1.2 g, 4.32 mmol) and hydrazine hydrate (6.27 mL) in ethanol (50 mL) was heated at 80 °C for 24 hours.
10. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, the residue was neutralized with 1N HCl to pH 7, and then extracted with ethyl acetate.
11. The organic phases were combined, dried and concentrated under reduced pressure and purified by silica gel column chromatography to give the target compound as a white solid.
