4-Methoxy-3-pyridinecarboxaldehyde

light yellow solid

Preparation of 4-Methoxypyridine-3-carboxaldehyde tert-Butyllithium (90.6 mL, 154 mmol ; 1.7 M in pentane) was added via cannula to a stirred solution of tetrahydrofuran (380 mL) under an atmosphere of nitrogen at room temperature. The reaction mixture was cooled to-78 °C before adding 2-bromomesitylene (11.3 mL, 74.1 mmol) dropwise. The reaction mixture was allowed to stir for 1 hour at-78 °C. To the reaction mixture at-78 °C was added 4- methoxypyridine (5.79 mL, 57 mmol) dropwise, and the resulting mixture was stirred at- 23 °C for 3 hours. The reaction mixture was then re-cooled to-78 °C and dimethylformamide (6.62 mL, 85.5 mmol) was added and stirring was continued for 1 hour at-78 °C. The reaction mixture was quenched slowly at-78 °C with saturated aqueous sodium chloride solution (100 mL) and allowed to warm to room temperature slowly. To the reaction mixture was added diethyl ether (200 rnL) and the layers were separated. The aqueous layer was extracted with diethyl ether (2 x 150 mL) and the combined organic layers were dried over potassium carbonate (20 g). The potassium carbonate was removed by filtration and washed with diethyl ether (100 mL) and the solvent removed under reduced pressure. The resulting crude 4-methoxy-3- pyridinecarboxaldehyde was purified by column chromatography (SiO2, 5: 95 ethanol: ethyl acetate) to give 4.79 g of the title intermediate as a yellow solid (61 percent yield; >98percent purity by'H NMR).To a solution of t-butyllithium in THF (1.7 M, 9.7 mL, 16.5 mmol, 2.1 eq) in THF (40 mL) maintained at -78 °C was added 2-bromomesitylene (1.6 g, 8.0 mmol, 1.3 eq) dropwise. The resulting solution was stirred for 1 h at -78 °C, then 4-methoxypyridine (681 mg, 0.63 mL, 6.2 mmol) was added and the mixture was warmed to -20 °C in an ice-salt bath. After stirring for 3 h at -20 °C, the mixture was cooled back to -78 °C and DMF (1.17 g, 16.0 mmol, 2.0 eq) was added. The reaction mixture was stirred for 1 h, quenched with brine at -78 °C and extracted with diethyl ether (3 × 100 mL). The combined organic extracts were dried over KTERT-BUTYLLITHIUM (90.6 mL, 154 mmol; 1.7 M in pentane) was added via cannula to a stirred solution of tetrahydrofuran (380 mL) under an atmosphere of nitrogen at room temperature. The reaction mixture was cooled to-78°C before adding 2-bromomesitylene (11.3 mL, 74.1 mmol) dropwise. The reaction mixture was allowed to stir for 1 hour at- 78°C. To the reaction mixture at-78°C was added 4-methoxypyridine (5.79 ML, 57 mmol) dropwise, and the resulting mixture was stirred AT-23°C for 3 hours. The reaction mixture was then re-cooled to-78°C and DIMETHYLFORMAMIDE (6.62 mL, 85.5 mmol) was added and stirring was continued for 1 hour AT-78°C. The reaction mixture was quenched slowly AT-78°C with saturated aqueous sodium chloride solution (100 mL) and allowed to warm to room temperature slowly. To the reaction mixture was added diethyl ether (200 mL) and the layers were separated. The aqueous layer was extracted with diethyl ether (2 x 150 mL) and the combined organic layers were dried over potassium carbonate (20 g). The potassium carbonate was removed by filtration and washed with diethyl ether (100 mL) and the solvent removed under reduced pressure. The resulting crude 4-methoxy-3- pyridinecarboxaldehyde was purified by column chromatography (SiO2, 5: 95 ethanol: ethyl acetate) to give 4.79 g of the title intermediate as a yellow solid (61percent yield; >98percent purity by'H NMR). Analytical Data : HNMR (300 MHz, CDCL) 8 10.43 (s, 1H, CHO), 8.87 (s, 1H, ArH), 8.63 (d, 1H, J= 6, ARH), 6.92 (d, 1H, J= 6, ART), 3.98 (s, 3H, CH30).SYNTHESIS OF AZAINDOLE AND AZAINDOLE RELATED COMPOUNDS [024O] In this example, various preferred azaindole and azaindole-related compounds are prepared. LiAIH4, THF reflux [00567] Ethyl alpha-Azido-beta-(4-methoxypyrid-3-yl)-acrylate 2. A homogeneous mixture of 3-formyl-4-methoxypyridine 1 (7.0 g, 54.7 mmol) and ethyl azidoacetate (5.0 g, 36.4 mmol) in anhydrous EtOH (50 mL) was added through a dropping funnel to a well-stirred solution containing Na (0.1.24 g, 54.7 mmol) in anhydrous EtOH (30 mL) under N2 at -15 0C. The mixture was stirred at that temperature for 4 h. During this time the precipitated solid was filtered and washed with ice cooled ethanol (30 mL). The compound was dried under vacuum oven for 3 h to get pure title compound 2 as white crystalline solid. Mp 92-95 0C; Yield: 4.8 g, 53%; ESI MS: m/z 248.9 (M+1).A homogeneous mixture of 3-formyl-4-methoxypyridine 1 (7.0 g, 54.7 mmol) and ethyl azidoacetate (5.0 g, 36.4 mmol) in anhydrous EtOH (50 mL) was added through a dropping funnel to a well-stirred solution containing Na (0.1.24 g, 54.7 mmol) in anhydrous EtOH (30 mL) under N2 at -15 C. The mixture was stirred at that temperature for 4 h. During this time the precipitated solid was filtered and washed with ice cooled ethanol (30 mL). The compound was dried under vacuum oven for 3 h to get pure title compound 2 as white crystalline solid. Mp 92-95 C.; Yield: 4.8 g, 53%; ESI MS: m/z 248.9 (M+1).

Molecular Weight:137.14
XLogP3:0.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:137.047678466
Monoisotopic Mass:137.047678466
Topological Polar Surface Area:39.2
Heavy Atom Count:10
Complexity:116
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes