2,4-Dimethoxypyridine

Freshly prepared sodium methoxide (24 g, 0.44 mol) was added to a solution of 2, 4-dichloropyridine (15 g, 0.10 mol) in anhydrous N-methyl-2-pyrrolidone (80 mL). The resulting mixture was stirred at 120° C for 6h. The mixture was then cooled to room temperature, diluted with ethylacetate (800 mL) and washed with water. The organic layer was dried over Na2SO4 and concentrated to give 2, 4-dimethoxypyridine (4) as a colourless oil, which was pure enough to use in the next step: Yield 11.2 g (80percent);1H NMR (400 MHz, DMSO-d6): δ 3.80 (s, 3H), 3.84 (s, 3H), 6.33 (d, J =2.0 Hz, 1H), 6.60 (dd, J = 2.0 Hz, J = 5.6 Hz, 1H), 7.97 (d, J = 5.6 Hz, 1H);13C NMR (100 MHz, DMSO-d6): δ 167.5, 165.4, 147.4, 106.1, 93.8, 55.3, 53.1; HRMS (ESI) m/z calcd for C7H10NO2: [M + H]+: 140.0706; found:140.0707[0884] XXIII-1 (15 g, 0.1 mol) was dissolved in anhydrous DMF (80 mL), and then freshly prepared sodium methoxide (24 g, 0.44 mol) was added. The resulting mixture was stirred at 110-120° C. for 12 hrs under N[0884] XXIII-1 (15 g, 0.1 mol) was dissolved in anhydrous DMF (80 mL), and then freshly prepared sodium methoxide (24 g, 0.44 mol) was added. The resulting mixture was stirred at 110-120° C. for 12 hrs under NXXIII-1 (15 g, 0.1 mol) was dissolved in anhydrous DMF (80 mL), and then freshly prepared sodium methoxide (24 g, 0.44 mol) was added. The resulting mixture was stirred at 110 - 120 °C for 12 hrs under N2. Cooled to rt, diluted with EA (800 mL) and washed with water and brine, dried over Na2SO4, concentrated. The residue was purified by flash column chromatography (PE/EA = 10:1) to give XXIII-2 (7.5 g, 54percent yield) as a colorless oil.EXAMPLE 33 : 1-(4-Chloro-2-fluorobenzyl)-4-inethoxy-5-(4-inethoxyphenyl) pyridin-2(1H)-one (Final Compound 9-18)Step 1 : 2, 4-Dimethoxypyridine According to Scheme 23 Step 1 : To a solution of sodium methoxide (30percent in MeOH, 2eq, 35mmol) was added 2-chloro-4-methoxypyridine (leq, 17.0mmol, 2.50g). The reaction was refluxed overnight. The reaction was allowed to cool, poured onto water (10mL) and extracted with CH2Cl2 (3xl0mL). The combined organic fractions were dried (Na2SO4), filtered and concentrated under reduced pressure to afford 2, 4- dimethoxypyridine (lO.lmmol, 1.40g, 58percent) as a colorless oil. The crude product was reacted on. LC (XTerra RP18, 3.5μm, 3.0x50mm Column): RT = 1.40min; MS m/z (CI) [MH]+= 140.General procedure: An aromatic compound (0.50 mmol) was dissolved in 2, 2, 2-trifluoroethanol (3 mL) including a small portion of dichloromethane. MesI(OH)OTs (217 mg, 0.50 mmol) was then added in one portion at room temperature. After stirring the mixture for 3 h, methanol (~3 mL) was added, and the solvents were evaporated. The crude product 1-OTs was then precipitated by adding diethyl ether with stirring. The precipitate was filtered and dried in vacuo to give a pure iodonium(III) salt 1-OTs in powder form. The solvents recovered by evaporation could be reused repeatedly after distillation.General procedure: A stirred solution of iodomesitylene (123 mg, 0.50 mmol) andwet m-chloroperbenzoic acid (69% purity, 126 mg, ~0.50 mmol) in a mixed solvent of 2, 2, 2-trifluoroethanol (2.5 mL) and dichloromethane (0.25 mL) was stirred for 30 min at room temperature. 1, 3, 5-Trimethoxybenzene (84 mg, 0.50 mmol) and p-TsOH*H2O (95 mg, 0.50 mmol) were then added, and the resulting solution was stirred for 2 h. After treatment with methanol (~2 mL), the solvents were evaporated, and the crude product 1a-OTs was further purified by trituration with diethyl ether. The precipitate was collected and dried under vacuum to give the pure salt 1a-OTs (204 mg, 0.35 mmol) in 70% yield.

Molecular Weight:139.15
XLogP3:1.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:139.063328530
Monoisotopic Mass:139.063328530
Topological Polar Surface Area:31.4
Heavy Atom Count:10
Complexity:97.6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes