Application of 2-chloro-4-nitro-5-methylpyridine_Industrial additives

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.