[Synthesis]
General procedure for the synthesis of ethyl 3-bromoisonicotinate and 3-bromopyridine-4-amide from ethyl chloroformate and 3-bromoisonicotinic acid: ethyl chloroformate (0.58 g, 5.4 mmol) was added dropwise to a cooled mixture of 3-bromoisonicotinic acid (1.00 g, 4.6 mmol), anhydrous THF (15 mL) and anhydrous triethylamine (1.0 mL). The mixture was stirred at 0°C for 1 hour and then ammonia was bubbled through the suspension for 15 minutes. The mixture was filtered and the solids were washed with hot acetone. The solvent was evaporated from the combined filtrate and washings and recrystallized from ethanol to give 3-bromopyridine-4-amide (777 mg, 78%) as an off-white powder: melting point 149-150°C; 1H NMR (CDCl3) δ 7.48 (1H, d, J = 4.8 Hz, 5-H), 7.88 (1H, br, NH), 8.11 (1H, br, NH) , 8.65 (1H, d, J = 4.8 Hz, 6-H), 8.84 (1H, s, 2-H); 13C NMR (CDCl3) δ 116.82 (3-C), 122.73 (5-C), 146.02 (4-C), 148.58 (6-C), 151.68 (2-C), 167.03 (C=O); MS m/z 224.9469 (M + Na)+ (C6H581BrN2NaO requires 224.9457), 222.9485 (M + Na)+ (C6H58FBrN2NaO, requires 222.9477). Evaporation of the solvent from the mother liquor gave ethyl 3-bromoisonicotinate (60 mg, 5%) as a yellow liquid: 1H NMR (CDCl3) δ 1.41 (3H, t, J = 7.2 Hz, Me), 4.43 (2H, q, J = 7.3 Hz, CH2), 7.59 (1H, d, J = 4.9 Hz, 5-H), 8.59 (1H, d, J = 4.9 Hz, 6-H), 8.83 (1H, s, 2-H); 13C NMR (CDCl3) δ 14.04 (Me), 62.33 (CH2), 118.71 (3-C), 124.15 (5-C), 139.34 (4-C), 148.41 (6-C), 153.64 (2-C), 164.47 (C = O); MS m/z 253.9623 (M + Na) + (C8H88AlBaNaO2 requires 253.9611), 251.9638 (M + Na) + (C8H89BrNNaO2 requires 251.9631), 224.9469 (M + H) + (C6H581BrN2O requires 224.9457), and 222.9485 (M + H) + (C6H579BrN2O requires 222.9477). |