4-IODO-2-PYRIDONE

General procedure: To 4b/c/d (prepared above) and sodium acetate (2.0 eq.) in acetic acid (1.0M)was heated at 150°C in a sealed tube for 72h. The mixture was cooled to r.t. andconcentrated under reduced pressure. The residue was partitioned between ethylacetate (3 mL/mmol) and cold water (3mL/mmol). The aqueous layer was extractedwith ethyl acetate (3mL/mmol; 4x). The combined organic layers were successivelywashed with sat. NaHCO3 (1 mL/mmol), brine, dried (Na2SO4), filtered andconcentrated under reduced pressure. The crude material was purified by flashchromatography on silica gel to give products 1b/c/d, and details of individualcompounds are provided below.A mixture of 2-chloro-4-iodopyridine (4.943 g, 20.6 mmol) and formic acid(88percent, 10 mL) was stirred at 105° C. for 21 h. The excess of formic acid was removed in vacuo, and the mixture was quenched with 2 M aq NaStep i: 4-iodopyridin-2(lH)-one General procedure: A 25 mL Teflon-sealed flask was charged with the corresponding 2-pyridone 1 (0.5 mmol), diaryliodonium salt 2 (0.75 mmol, 1.5 equiv), and Cs2CO3 (0.75 mmol, 1.5 equiv) under an air atmosphere. DCE (5mL) was added to the flask. Then, the reaction vessel was sealed witha Teflon cap. The reaction mixture was stirred at 120 C until the2-pyridone 1 was consumed completely (monitored by TLC). At thistime, the solvent was removed in vacuo and the residue was purifiedby flash column chromatography (the crude residue was dry loadedon silica gel, 1:20 to 1:1, EtOAc/PE) to provide the desired products 3and 4 (Scheme 2, Tables 2, 3).1-Phenylpyridin-2(1H)-one (3aa)19Yield: 0.054 g (63%); orange solid; mp 94-95 C.1H NMR (500 MHz, CDCl3): delta = 7.50-7.47 (m, 2 H), 7.43-7.36 (m, 4 H), 7.34 (d, J = 8.5 Hz, 1 H), 6.66 (d, J = 10.5 Hz, 1 H), 6.25 (t, J = 7.0 Hz, 1 H).13C NMR (125 MHz, CDCl3): delta = 162.3, 140.9, 139.8, 137.9, 129.2, 128.4, 126.4, 121.8, 105.8.1-Cyclopropyl-4-Iodo-1-methyl-1, 2-dihydropyridin-2-one 4-Iodo-1, 2-dihydropyridin-2-one (500 mg, 2.26 mmol), MeI (296 uL, 4.75 mmol) and K2CO3 (688 mg, 4.98 mmol) were suspended in MeCN (20 mL) and stirred for 18 h. The reaction mixture was filtered and the solvents removed in vacuo. The residue was purified by column chromatography to give the title compound (411 mg, 77.3%) as a white solid. LCMS (ES+): 236.0 [MH]+. HPLC: Rt 4.48 min, 99.6% purity.

Molecular Weight:221.00
XLogP3:0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:220.93376
Monoisotopic Mass:220.93376
Topological Polar Surface Area:29.1
Heavy Atom Count:8
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes