3,5-Dibromo-1-methylpyridin-2(1H)-one

A solution of 3, 5-dibromo-1 H-pyridin-2-one (5 g, 19.8 mmol) in DMF (170 ml), KA 1-L round-bottomed flask equipped with a magnetic stirrer was charged with 3, 5-dibromo-lH-pyridin-2-one (7.0 g, 27.7 mmol), anhydrous DMF (280 mL) and powdered potassium carbonate (-350 mesh, 8.4 g, 61.1 mmol), and the A 1-L round-bottomed flask equipped with a magnetic stirrer was charged with 3, 5-dibromo-lH-pyridin-2-one (7.0 g, 27.7 mmol), anhydrous DMF (280 mL) and powdered potassium carbonate (-350 mesh, 8.4 g, 61.1 mmol), and the Example 1N-{3-[5-(6-Amino-pyridin-2-ylamino)-l-methyl-6-oxo-l, 6-dihydro-pyridin-3-yl]- 2-methyl-phenyl}-4-ter/-butyl-benzamide (3) General procedure: A Schlenk tube was charged with the 2-pyridone substrate (1.0 mmol) [in the case of a liquid substrate, this was added neat after the solvent], [Ir(cod)(OMe)]2 (6.6 mg, 0.01 equiv), 4, 4′-di-tert-butyl-2, 2′-dipyridyl (5.4 mg, 0.02 equiv) and bis(pinacolato)diboron (178 mg, 0.70 equiv). After purging with nitrogen, deoxygenated and anhydrous THF (1.4 mL) was added and the reaction mixture was heated at reflux for 48 h (in cases where full conversion occurred after 24 h, the reaction was halted at that time). The volatile materials were then removed under reduced pressure and the crude product was dissolved in MeOH (2.5 mL) and a solution of CuBr2 (670 mg, 3.0 mmol) in H2O (2.5 mL) was added. The reaction mixture was heated at 80 °C for 18 h under air, cooled to r.t., diluted with NH4OH (5 mL, 15percent aq) and extracted with CH2Cl2 (5 × 5 mL). The combined extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification of the crude reaction mixture by flash column chromatography on silica gel afforded the desired product. Table 1 shows the product distributions of 2–5 but no attempt was made to optimise monosubstitution (vs. disubstitution) in the case of 1b or 1c. According to General Procedure 1, analysis of the 1H NMR spectrum ofthe crude reaction mixture showed a conversion of 100percent. Products 5-bromo-1-methylpyridin-2(1H)-one (3b), 4-bromo-1-methylpyridin-2(1H)-one (2b), 4, 6-dibromo-1- methylpyridin-2(1H)-one (4b) and 3, 5-dibromo-1-methylpyridin-2(1H)-one (5b) were generated in a 35:5:39:21 ratio. Purification by flash column chromatography on silica gel (n-hexane–EtOAc, 70:30 to EtOAc, 100percent) gave an inseparable 95:5 mixture of 5-bromo-1-methylpyridin-2(1H)-one (3b) and 4-bromo-1-methylpyridin-2(1H)-one (2b) (71 mg, 38percent) as an orange oil. 2b (minor component) Rf = 0.24 (EtOAc). 1H NMR (400 MHz, CDCl3): δ = 7.11 (d, J = 7.5 Hz, 1 H), 6.79 (d, J = 2.0 Hz, 1 H), 6.28 (dd, J = 2.0, 7.5 Hz, 1 H), 3.50 (s, 3 H). The spectroscopic properties of this compound were consistent with data available in literature. 3b (major component) Rf = 0.24 (EtOAc).1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 2.5 Hz, 1 H), 7.33 (dd, J = 2.5, 9.5 Hz, 1 H), 6.46 (d, J = 9.5 Hz, 1 H), 3.50 (s, 3 H). The spectroscopic properties of this compound were consistent with data availablein literature.19a4, 6-Dibromo-1-methylpyridin-2(1H)-one (4b) Yield: 58 mg (22percent); off-white solid; Rf = 0.59 (EtOAc). IR (neat): 3111, 2922, 2851, 1650, 1566, 1495 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.75 (s, 1 H), 6.66 (s, 1 H), 3.68 (s, 3 H).13C NMR (100 MHz, CDCl3): δ = 161.5, 134.8, 128.3, 120.7, 114.4, 36.4.HRMS-ESI: m/z [M + H]+ calcd for C6H679Br2NO: 265.8811; found:265.8799.3, 5-Dibromo-1-methylpyridin-2(1H)-one (5b)Yield: 28 mg (11percent); white solid; Rf = 0.51 (EtOAc). 1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 2.0 Hz, 1 H), 7.43 (d, J = 2.0 Hz, 1 H), 3.58 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 158.0, 143.8, 137.5, 117.4, 96.5, 39.0. The spectroscopic properties of this compound were consistent withthe data available in literature.

Molecular Weight:266.92
XLogP3:1.7
Hydrogen Bond Acceptor Count:1
Exact Mass:266.87174
Monoisotopic Mass:264.87379
Topological Polar Surface Area:20.3
Heavy Atom Count:10
Complexity:232
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes