2-Methyl-3-pyridinecarboxamide

White solid

Solid

2-methylnicotinamide is a pyridinecarboxamide that is nicotinamide substituted by a methyl group at C-2. It has a role as a metabolite. It derives from a nicotinamide.

29) 2-methylnicotinamideTo a solution of 2-methylnicotinic acid (0.537 mg, 3.9 mmol) in 20 mL of DMF at 0 I chloride (1.90 mL, 21.8 mmol) was added to 2-methyl nicotinic acid (1.50 g, 10.9 mmol) in anhydrous dichloromethane (20 mL) with triethylamine (1.6 mL, 11.5 mmol) and the reaction mixture was kept at room temperature overnight before the solvent was removed. THF was added to the residue and ammonia gas was bubbled through for 2 h. The THF was removed and the residue was dissolved into methanol and water and the pH was adjusted to 10.0 with potassium carbonate. The mixture was concentrated. After column chromatography the desired amide was isolated (1.10 g, 73.8percent). [0439] NaH (0.428 g, 10.7 mmol, 60percent in mineral oil) was added to 4-hydroxy-3, 5-dimethylbenzonitrile (1.50 g, 10 mmol) in anhydrous DMF (8 mL). Benzyl bromide (1.83 g, 10.7 mmol) was added and the reaction was kept at room temperature overnight. The reaction mixture was poured into water. The isolated solid was further washed with hexane to yield the desired ether building block (2.0 g, 84.3percent). It was used in the next reaction without further purification. The above amide (0.65 g, 4.77 mmol) in anhydrous THF (15 mL) was added drop-wise to BuLi (7.5 mL, 1.60 M) at −20° C. The reaction mixture was kept at this temperature for 1 h and then the above ether building block (1.13 g, 4.77 mmol) in THF (20 mL) was added drop-wise at −20° C. and the reaction was stirred for 1.5 h. The reaction temperature was increased to room temperature and continued for a further 1 h. Water (20 mL) was added and the mixture was stirred for a while before the solvent was removed and the residue was purified by column chromatography to yield the desired intermediate (0.50 g, 29.4percent). A 50 mL flask was charged with the above described intermediate (0.50 g, 0.0014 mol) and pyridine hydrogen chloride (2.4 g, 0.014 mol) and the mixture was heated to 180° C. for 1.5 h. The mixture was cooled and poured into methanol (4 mL), then filtered. The collected solid was further washed with ethyl acetate and dried to give 7-(4-hydroxy-3, 5-dimethylphenyl)-1, 6-naphthyridin-5(6H)-one (350 mg, 82.7percent) as an HCl salt. Selected data: MS (ES) m/z: 266; MP >350° C.[0620] To the solution of XI-1 (10 g, 73 mmol, 1 eq) in 50 mL of DCM was added 15 mL of oxalyl chloride (adding a drop of DMF). The mixture was stirred for 18 hrs at rt. All the volatiles were removed under reduced pressure. The residue was dried and used directly for the next step (11.3 g, 100percent yield). The solid was dissolved in 30 mL of DCM and added into 200 mL of CHTo the solution of X-1 (10 g, 73 mmol, 1 eq) in 50 mL of DCM was added 15 mL of oxalyl chloride (adding a drop of DMF). The mixture was stirred for 18 hrs at rt. All the volatiles were removed under reduced pressure. The residue was dried and used directly for the next step (11.3 g, 100percent yield). The solid was dissolved in 30 mL of DCM and added into 200 mL ofCH2C12-NH3 at -30°C. The mixture was stirred for 18 hrs. LCMS analysis showed the reaction completed. All the volatiles were removed under reduced pressure to afford X-2 (7 g, 71percent yield), which was used directly for the next step. ‘H NMR (DMSO-d6, 400 MHz): ö 8.45 (m, 1H), 7.93 (s, 1H), 7.71 (d, J= 7.6 Hz, 1H), 7.54 (s, 1H), 7.23 (m, 1H), 2.48 (s, 3H).

Molecular Weight:136.15
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:136.063662883
Monoisotopic Mass:136.063662883
Topological Polar Surface Area:56
Heavy Atom Count:10
Complexity:136
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes