3-BROMO-1-METHYLPYRIDIN-2(1H)-ONE

General procedure: In a dry Schlenk tube 6-methyl-2(1H)-pyridone (1) (3.43 g, 31.44 mmol) was dissolved in 50 mLof 1, 4-dioxane and KOt-Bu (8.69 g, 62.88 mmol) was added. The mixture was stirred at 100 °C for 2 h, then cooled down to rt, MeI (19.6 mL, 314.41 mmol) was added dropwise and the mixture was stirred at 80 °C for 16 h. The solvent was removed under reduced pressure and the residue was separated between DCM and water. The extraction was performed using DCM (3×) and the combined organic phases were dried over MgSOExample 19 To a stirred solution of 3-bromopyridin-2(1H)-one (44-1) (1 g, 5.74 mmol) in dry DMF (4 mL ) at 0°C, was added NaH (343 mg, 8.61 mmol) and the mixture was stirred for 30 minutes followed by addition of iodomethane (976 mg, 6.88 mmol) and stirring for another 2 h. After completion of reaction as monitored by TLC, the mixture was partitioned between ethyl acetate and brine. The organic extracts were dried over sodium sulfate, concentrated, and the residue was purified over silica to obtain 3-bromo-1-methylpyridin-2(1H)-one (44-2) (800 mg, 4.25 mmol, 74.7 percent) as a solid. LC MS: ES+ 188.0.At 40° C., a mixture of 5.0 g (28.7 mmol) of 3-bromo-2-hydroxypyridine, 17.9 ml (0.287 mol) of iodomethane, 1.06 g (2.87 mmol) of tetra-n-butylammonium iodide and 19.9 g (0.144 mol) of potassium carbonate is stirred in 60 ml of toluene for 15 hours. 250 ml of water are then added, and the reaction mixture is extracted with ethyl acetate. Methyl iodide (1.5 mL, 24.14 mmol) was added to a suspension of potassium carbonate (1668 mg, 12.07 mmol), TBAI (89 mg, 0.24 mmol) and 3-bromopyridin-2-ol (420 mg, 2.4 14 mmol) in toluene (15 mL). The reaction mixture was heated to 40 °C for 17 hours. The mixture was partitioned between DCM and water and the combined extracts dried (hydrophobic fit) and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluted with 0-70percent petrol/ethyl acetate to afford 3 -bromo- 1- methylpyridin-2(1H)-one, Intermediate 5 (390 mg, 86 percent).‘H NMR (400 MHz, DMSO-d6) & 3.50 (s, 3 H) 6.17 (t, J=7.07 Hz, 1 H) 7.78 (dd, J=6.82, 1.77 Hz, 1 H) 7.90 (dd, J=7.33, 1.77 Hz, 1 H)20.2) 3-Bromo-1-methyl-1 H-pyridin-2-one (intermediate 63): To a solution of 3-bromo-pyridin-2-ol (2.06g, 11.5 mmol.) in DMF (10 ml) was added NaH (60percent, 0.5Og, 12.64 mmol.) portionwise at OA mixture of iodomethane (1.22 g), 3-bromopyridin-2-ol (500 mg), potassium carbonate (1.19 g) and N, N-dimethylformamide (2 mL) was stirred at 80°C for 1 hr. A mixture of 2-hydroxy-3-bromopyridine (Aldrich, 967 mg, 5.56 mmol), potassium carbonate(1536 mg, 11.12 mmol) and iodomethane (0.521 mL, 8.34 mmol) in DMF (10 mL) was stirred for1 h at rt, diluted in EtOAc/water, and extracted twice with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and the filtrate was concentrated. The residue was purified by silica gel column chromatography (50percent EtOAc/hexane) to afford the title compound (757 mg) as a yellow oil. Rf= 0.11 (50percent EtOAc/hexane); Rt: 0.50 mm (LC-MS 1);MS mlz: 188.0 [M](LC-MS 1).

Molecular Weight:188.02
XLogP3:1.3
Hydrogen Bond Acceptor Count:1
Exact Mass:186.96328
Monoisotopic Mass:186.96328
Topological Polar Surface Area:20.3
Heavy Atom Count:9
Complexity:195
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes