Application background and overview of 2-chloro-4-nitro-5-methylpyridine
2-Chloro-4-nitro-5-methylpyridine can be used as a pharmaceutical synthesis intermediate, such as the preparation of compound 2-(4-bromophenyl)-6-chloro-2,3-dihydrofuran [3,2-c]pyridine and 6-chloro-2-(1-methyl-1H-indol-2-yl)-2,3-dihydrofuran[3,2-c]pyridine.
Applications of 2-chloro-4-nitro-5-methylpyridine
Application of 2-chloro-4-nitro-5-methylpyridine Application 1. Preparation of 2-(4-bromophenyl)-6-chloro-2,3-dihydrofuran [3, 2-c]pyridine
To 1.00mmol nitroaniline, 1.20mmol benzaldehyde, 1.5mmol Hünig base, and 300mg (1.74mmol) 2-chloro-4-nitro-5-methylpyridine cyclization, add THF solution, carbonic acid Sodium heated the resulting mixture to 60°C for 2.0 h; after cooling to room temperature, the reaction was quenched with saturated NaHCO3, the solution was extracted with EtOAc, and dried over MgSO4 , and concentrated under reduced pressure. The residue was purified by silica gel chromatography to give 2-(4-bromophenyl)-6-chloro-2,3-dihydrofuran[3,2-c]pyridine. 1HNMR (500MHz, CDCl3) d3.18 (dd, 1H, J¼15.8and7.8Hz), 3.68 (dd, 1H, J¼15.8and9.6Hz), 5.89 (dd, 1H, J¼9.6and7.8Hz), 6.85 (s, 1H), 7.25 (d, 2H, J¼8.3Hz), 7.55 (d, 2H, J¼8.3Hz), 8.13 (s, 1H); 13CNMR (125MHz, CDCl3)d34.8, 86.0, 105.8, 122.6, 123.2, 127.3, 132.0, 139.1, 144.6, 151.1, 167.9.
Application of 2-chloro-4-nitro-5-methylpyridine Application 2: Preparation of 6-chloro-2-(1-methyl-1H-indol-2-yl)-2, 3-Dihydrofuran[3,2-c]pyridine
Mix 340 mg (1.97mmol) 2-chloro-4-nitro-5-methylpyridine, 2.56mL (2.56mmol) benzaldehyde and 383mg (2.96mmol) Hünig’s base, add THF solution, and The mixture was heated to 60°C and reacted for 2.0 h; after cooling to room temperature, the reaction was quenched with saturated NaHCO3, the solution was extracted with EtOAc, dried over MgSO4, and dried in Concentrate under reduced pressure. The residue was purified by silica gel chromatography to give 6-chloro-2-(1-methyl-1H-indol-2-yl)-2,3-dihydrofuran[3,2-c]pyridine as a colorless solid: mp250 ℃.
1HNMR (500MHz, CDCl3) d3.67 (d, 2H, J¼9.2Hz), 3.86 (s, 3H), 6.20 (t, 1H , J¼9.2Hz), 6.62 (s, 1H), 6.79 (s, 1H), 7.15 (t, 1H, J¼7.7Hz), 7.30 (m, 1H), 7.39 (d, 1H, J¼8.4Hz), 7.63 (d, 1H, J¼7.7Hz), 8.21 (s, 1H); 13CNMR (125MHz, CDCl3) d30.3, 31.1, 79.9, 101.4, 106.1 , 109.3, 120.0, 121.2, 122.8, 123.5, 126.6, 135.8 Heavy magnesium carbonate, 138.5, 144.5, 151.1, 167.4.
References
[1] Kuethe, Jeffrey T. “A concise synthesis of functionalized 2, 3-dihydrofuro [3, 2-b],[3, 2-c], and [2, 3-b] pyridines.” Tetrahedron 75.34 (2019): 130446.
