Methyl 2-aminonicotinate

Off white powder

Concentrated sulfuric acid (96percent, 144 mL, 2.69 mol, 18.6 equiv) was added dropwise to a stirred suspension of 5 (20.0 g, 0.145 mol) in MeOH (228 mL, 7.12 mol, 49.2 equiv) maintained at 0 C. The mixture was irradiated at atmospheric pressure under microwaves (power input 300 W) at 60 C for 1.5 h. The light brown mixture was poured onto iced water, maintained at 0 C and carefully quenched by adding solid Na2CO3 portionwise until complete neutralization (pH>8). The aqueous layer was extracted three times with AcOEt. The combined organic layers were washed with brine and water and dried over MgSO4. Evaporation of the organic layer yielded the title compound 21 in analytically pure form (21.15 g, 93percent) as colourless needlesA mixture of 2-aminonicotinic acid (0.25 g, 1.80 mmol) and 1.80 mL of concentrated HExample 7 Synthesis of Compound 33 General Method for the SYNTHESIS of Compounds 26-44 [0096] This example illustrates Reaction Scheme IV. Preparation OF IVA : [0097] 2-Amino NICOTINIC acid (SOG, 0. 362 mole) was dissolved in 500ml methanol and treated with thionyl chloride (66MOL, 107. 6g, 0. 905MOLLE) dropwise over 30 min. Reaction mixture was heated to reflux for 3 days. Removed solvent under vacuum, residue taken up in chloroform, washed with 5percent HCl (50ml), 10percent sodium bicarbonate (50ml), water, and chloroform layer dried over sodium sulfate (ANH). Removed solvent to give 27G product (49. 1 percent yield).Example 7 Synthesis of Compound 33 General Method for the SYNTHESIS of Compounds 26-44 [0096] This example illustrates Reaction Scheme IV. Preparation OF IVA : [0097] 2-Amino NICOTINIC acid (SOG, 0. 362 mole) was dissolved in 500ml methanol and treated with thionyl chloride (66MOL, 107. 6g, 0. 905MOLLE) dropwise over 30 min. Reaction mixture was heated to reflux for 3 days. Removed solvent under vacuum, residue taken up in chloroform, washed with 5percent HCl (50ml), 10percent sodium bicarbonate (50ml), water, and chloroform layer dried over sodium sulfate (ANH). Removed solvent to give 27G product (49. 1 percent yield).Preparation Example A-2. 2-Amino-nicotinic acid (10.0g, 72.4mmol) was dissolved in a mixed solution of methanol (200mL) and sulfuric acid (10mL), and the solution was stirred under reflux for 35 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution at 0°C, which was extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by NH silica gel column chromatography to obtain the title compound (5.26g, 34.6mmol, 48percent) as a white solid. Synthesis of 2:A mixture of 1 (2.0 g, 14 mmol) in concentrated HContaining 13.8 g of 2-amino acid (0.1 mmol) of potassium carbonate and 27.6 g (0.2 mole, 2.0 eq.) Of dimethyl sulfoxide was heated to reflux, then the solution was cooled to ambient temperature, was added 14.2 g of iodine methane (0.1 mole, 1.0 eq) to the mixture, and the solution was stirred for 18 hours, the mixture was filtered and concentrated to give a residual material containing 0.1percent aqueous ammonia (5/95 ethanol / dichloromethane) was eluted as after filtration of the liquid silicone pad and the resulting solution was concentrated, the residue was suspended in ether, filtered and dried to give 2-amino-nicotinic acid methyl ester (10.8 g, 71percent yield). Analysis of results:1 ) A suspension of 2-aminonicotinic acid (833 mg, 6.00 mmol) and potassium carbonate (912 mg, 6.60 mmol) in dimethylformamide (DMF, 8.5 ml) was heated to reflux. The reaction mixture was cooled to room temperature and 415 μΙ of iodomethane (6.60 mmol) were added. The mixture was then refluxed under stirring for 18 h; after subsequent cooling, the mixture was finally filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (ethyl acetate/petroleum ether = 7/3). The isolated 2-aminonicotinic acid methyl ester was obtained in 58percent yield.1) A suspension of 2-aminonicotinic acid (833 mg, 6.00 mmol) and potassium carbonate (912 mg, 6.60 mmol) in dimethylformamide (DMF, 8.5 ml) was heated to reflux. The reaction mixture was cooled to room temperature and 415 μl of iodomethane (6.60 mmol) were added. The mixture was then refluxed under stirring for 18 h; after subsequent cooling, the mixture was finally filtered and the filtrate was concentrated under reduced pressure. The crude product was purified is by flash chromatography on silica gel (ethyl acetate/petroleum ether=7/3). The isolated 2-aminonicotinic acid methyl ester was obtained in 58percent yield.e) Preparation of Methyl 2-aminonicotinate; [00309] To a mixture of 2-aminonicotinic acid(n) (30.0 g 217 mmol) and 2-chloro1, 3-dimethyl imidazolinium chloride(55.2 g 326 mmol) in MeOH (750 ml) was added dropwise triethylamine (91 ml 652 mmol). The resultant mixture was stirred at room temperature for 1 h. The mixture was then evaporated under reduced pressure to afford a residue. The residue was purified by extraction with ethyl acetate (300 ml.x.2). The combined organic phase was washed with water (200 ml.x.2) and brine (200 ml). Dried over anhydrous sodium sulfate, filtered and concentrated to give an essentially pure methyl 2-aminonicotinate (31.3 g, yield 94percent). This compound was used in next step without further purification.

Molecular Weight:152.15
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:152.058577502
Monoisotopic Mass:152.058577502
Topological Polar Surface Area:65.2
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes