2-METHYLNICOTINALDEHYDE

A mixture of the 3-hydroxymethyl-2-methylpyridine (9.Og, 73.1mmol) and manganese (IV) dioxide (28.1g, 322mmol) in DCM (100ml) was heated at reflux for two days. The insolubles were removed by filtration through diatomaceous earth and the filter pad was washed with methanol / DCM. The solvent was removed from the filtrate by evaporation to give 2-methylpyridine-3-carboxaldehyde (7.5g, 85percent) as an oil; NMR Spectrum 2.78 (s, 3H), 7.43 (dd, IH), 8.15 (dd, IH), 8.66 (dd, IH).A mixture of the 3-hydroxymethyl-2-methylpyridine (9.Og, 73.1mmol) and manganese (IV) dioxide (28. Ig, 322mmol) in DCM (100ml) was heated at reflux for two days. The insolubles were removed by filtration through diatomaceous earth and the filter pad was washed with methanol / DCM. The solvent was removed from the filtrate by evaporation to give 2-methylρyridine-3-carboxaldehyde (7.5g, 85percent) as an oil; NMR Spectrum 2.78 (s, 3H), 7.43 (dd, IH), 8.15 (dd, IH), 8.66 (dd, IH).N-((4-chloro-2-methylphenyl)(phenyl)methyl)-2-(2-((2-methylpyridin-3-yl)methyl)benzofuran-5- yl)acetamidea) 2-methylnicotinaldehydeTo a stirred solution of (2-methylpyridin-3-yl)methanol (200 mg, 1.6 mmol) in CH(a) 2-methyinicotinaidehyde: To a stirred solution of (2-methyipyridin-3-yl)methanoi (200 mg, 1.6 mmol) in CH2CI2 (10 mL) was added Mn02 (200 mg, 2.3 mmol). The mixture wasrefluxed overnight under rutrogcn. The solid was removed by fihration. After removal ofsolvent, the crude product was purified by silica gel column chromotography (petroleumether/EtOAc = i/i) to give the title compound (120 rug, 60percent) as a colorless liquid .LCMS-PI:122.0 [M+H]t R = 0.344 miii.To a solution of 3-bromo-2-methylpyridine (148; 10 g, 58.1 mmol) in THF (150 mL) was added n-BuLi (2.5 M, 25.6 mL) at -78 °C. The reaction mixture was stirred at this temperature for Ih. DMF (1.30 mL) was then added and the resulting reaction mixture was stirred for 1 h at -78 Example 21. Synthesis of 2-(2-methylpyridin-3-yl)-N-(thiazol-2-yl)-[l, 2, 4]triazolo[l, 5- a]pyridine-8-carboxamide (Compound 239):Step 1) Preparation of 2-methylnicotinaldehyde (89): To a solution of 3-bromo-2-methylpyridine (88; 10 g, 58.1 mmol) in THF (150 mL) was added n-BuLi (2.5 M, 25.6 mL) at -78 General procedure: The equimolar amount 6-(1H-indol-3-yl)-4, 5?-bipyrimidine-2-amine and substituted aldehydes were mixed in a round bottom flask containing 50 mL of ethanol, some droplets of glacial acetic acid were added to the mixture, and it was set on refluxing for 18 h. Solid product was observed on the completion of reaction that was filtered and dried under vacuum and recrystallized using proper solvent [50].

Molecular Weight:121.14
XLogP3:0.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:121.052763847
Monoisotopic Mass:121.052763847
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:103
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes