2-BROMO-3-FORMYLPYRIDINE

Yellow solid

To a cooled (–78 C) solution of diisopropylamine (20.4 g, 28.0 mL, 0.202 mol) in dry THF (400 mL), n-BuLi (0.192 mol, 58.0 mL, 3.3 M in hexane) was added at this temperature. The mixture was stirred at –78 C for 1 h, and a solution of 2-bromopyridine (25.3 g, 0.160 mol) in dry THF (150 mL) was added over 20 min. The reaction mixture was kept at –78 C for 90 min, and a cooled (–78 C) solution of DMF (35.0 g, 0.480 mol) in dry THF (25 mL) was added in one portion. The resulting mixture was stirred for additional 80 min at –78 C, then treated with NaH2PO4 (27.6 g, 0.230 mol in H2O (120 mL)), warmed to rt, and diluted with MeOt-Bu (500 mL). The organic phase was separated, washed with brine (2100 mL), dried over Na2SO4, and concentrated in vacuo. The crude product was triturated with pentane. After decantation of the solvent, the remaining solid was recrystallized from hexanes. Yield 16.7 g, 56percent. Yellowish solid. Mp 67–69 C. 1H NMR (400 MHz, CDCl3), δ: 10.35 (s, 1H), 8.57 (dd, J = 4.7, 2.1 Hz, 1H), 8.17 (dd, J = 7.6, 2.1 Hz, 1H), 7.44 (ddd, J = 7.6, 4.7, 0.6 Hz, 1H). 13C NMR (101 MHz, CDCl3), δ: 190.4, 154.0, 144.9, 137.5, 130.1, 123.0. Anal. Calcd. for C6H4BrNO: C, 38.74; H, 2.17; N, 7.53; Br, 42.96. Found: C, 38.58; H, 2.08; N, 7.57; Br, 42.69.According to the literature, 16 a dry and argon-flushed Schlenk flask equipped with a magnetic stirring bar and a septum was charged with a solution of LDA (30.0 mmol, 0.5 M in THF) and cooled to –78 °C. 2-Bromopyridine (7.9 g, 10.0 mmol) was added dropwise to the cooled solution. The resulting mixture was stirred for 1 h at –78 °C. DMF (2.9 g, 40.0 mmol) was then added and the mixture stirred for 1h at –78 °C. The resulting solution was quenched with sat. aq NH4Cl (40 mL), extracted with EtOAc (3 × 80 mL), and the combined organic phases were dried (anhyd MgSO4). After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (i-hexane/EtOAc, 8:2 + Et3N 2percent) yielding 2-bromo-3-pyridine-carboxaldehyde as a colorless oil (1.0 g, 54percent).1H NMR (400 MHz, CDCl3): δ = 10.34 (1 H, s), 8.60 (dd, J = 4.5, 2.1 Hz, 1H), 8.19 (dd, J = 7.9, 2.1 Hz, 1 H), 7.46 (dd, J = 7.9, 4.5 Hz, 1 H).A mixture of 4d (2.15 g, 6.52 mmol) and CaCOTo a well stirred solution of 2-bromo-3-(dibromomethyl)-pyridine 2 (2.12 g, 6.56mmol, 1.0 equiv) in water (15 mL) calcium carbonate (1.5 g, 15.0 mmol, 2.2 equiv)was added in one portion. After addition, the resulted reaction mixture was stirred at100 for 7 h. The reaction mixture was cooled to room temperature and extractedwith EtOAc (20.0 mL × 3). The combined organic extracts were dried over anhydrousNa2SO4 and concentrated under reduced pressure. The residue was purified by flashchromatography on silica gel (eluent: EtOAc / petroleum ether = 1:7) to affordcompound 3 (0.75 g, 60percent yield) as white solid. 1H NMR (CDCl3): 10.35 (s, 1H), 8.60-8.62 (m, 1H), 8.19-8.21 (m, 1H), 7.46 (dd, J=4.8Hz, 2.0Hz, 1H).Intermediate 3: lH-Pyrrolo [2, 3-6] pyridine-2-carbaldehydeStep a: 2-bromonicotinaldehyde[0450] ft-BuLi (2.5 M solution, 42.0 mL, 0.105 mol) was added to a solution ofdiisopropylamine (15.5 mL, 0.11 mol) in THF (180.0 mL) at -78°C. After the mixture was stirred for 10 min, a solution of 2-bromopyridine (15.8 g, 0.10 mol) in THF (20.0 mL) was added dropwise and the mixture was stirred at -78°C for 2 h. Then HC0

Molecular Weight:186.01
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:184.94763
Monoisotopic Mass:184.94763
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes