5-Methylpyridine-3-carboxaldehyde

Step 2. 5-methyl-3-pyridinecarboxaldehyde. A mixture of 5-methyl-3-pyridinemethanol (106 mg, 0.86 mmol) and activated MnO2 (376 mg) in methylenechloride (10 mL) was stirred at room temperature overnight. The black solid of MnO2 was removed by filtration. The filtrate was concentrated in vacuo to yield the title compound as an oil (100 mg, 85percent). 1H NMR (CDCl3): 10.10 (s, 1H), 8.89 (s, 1H), 8.68 (s, 1H), 7.98 (s, 1H), 2.45 (s, 3H)To a solution of N-methoxy-N, 5-dimethylnicotinamide (3.0 g, 16.65 mmol) in THF (50 mL) was added LAH (0.76 g, 19.98 mmol) at -78 °C, and the resulting mixture was stirred at -78 °C for 30 mins. TLC showed the reaction was completed. The reaction was quenched with sat.NH4C1 (100 mL), and the mixture was extracted with EtOAc (100 mL x2). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated to give the desired 5-methylnicotinaldehyde (2.0 g, yield: 99percent) as yellow oil.‘HNMR (400 MHz, CDC13): = 10.10 (s, 1H), 8.89 (s, 1H), 8.68 (s, 1H), 7.97 (s, 1H), 2.57 (s, 3H).To a solution of General procedure: To a solution of amine (1.0 equiv) in 1, 2-dichloroethane (0.1 M) were added aldehyde (1.2 equiv) and acetic acid (0.5 mL), the reaction mixture stirred at rt for 10 min, followed the addition of sodium triacetoxyborohydride (2.0 equiv). The reaction was stirred at rt under nitrogen for 18 h and concentrated. Sat. NaHCO3 (30 mL) was added and extracted with dichloromethane (20 mL x 3) and the combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography on silica gel eluting with 0-10% methanol/dichloromethane to give the desired product.To a solution of compound But-3-enenitrile (1.05 g, 15.74 mmol) in THF (30 mL) was added N2H4.H20 (0.826 g, 16.52 mmol) slowly at 0 C, and the resulting mixture was stirred room temperature for 16 hrs. Then to the reaction mixture was added 5 -methylnicotinaldehyde (2.0 g, 16.52 mmol). After stirring for 2.5 hrs, the reaction mixture was concentrated to dryness in vacuum. To the residue in n-Butanol (30 mL) was added MeONa (0.85 g, 15.74 mmol), and the mixture was heated to 120 C for 16 hrs. The reaction mixture was poured into iN HC1 (50 mL), and the mixture was extracted with EtOAc (100 mL x2). The aqueous layer was basified to pH = 14 and extracted with EtOAc (100 mL x2). The extracts were dried over Na2SO4, filtered and concentrated to give 3-methyl-1-((5-methylpyridin-3-yl)methyl)-1H-pyrazol-5-amine (0.75 g, yield: 24%) as brown oil.

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