METHYL2-AMINO-5-METHOXYBENZOATE

5-Methoxy-2-nitro-benzoic acid (3.2 g) was dissolved in N, N-dimethylformamide (60 ml). Potassium carbonate (5.61 g) and methyl iodide (5.05 ml) were added to the solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with an acetone-hexane system to give methyl 5-methoxy-2-nitro-benzoate (3.38 g, yield 99percent). Methyl 5-methoxy-2-nitro-benzoate (3.38 g) was dissolved in N, N-dimethylformamide (34 ml). Triethylamine(7 ml) and 20percent palladium hydroxide (340 mg) were added to the solution, and the mixture was stirred under a hydrogen gas atmosphere at room temperature overnight. The reaction mixture was filtered and was washed with chloroform. The solvent was removed by distillation under the reduced pressure, water was added to the residue, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine, was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with an acetone-hexane system to give methyl 2-amino-5-methoxy-benzoate (2.87 g, yield 99percent).A mixture of compound 21 (1.01 g, 4.77 mmol), Pd/C (10percent, 50.9 mg) and methanol (15 mL) wasstirred at room temperature under an atmosphere of hydrogen for 3 h. The mixture was filteredthrough Celite® and concentrated in vacuo to give the title compound as a yellow oil (0.860 g, 99percent); 1H NMR (300 MHz, CDCl3) δ 7.34 (d, J = 3.0 Hz, 1H, H3), 6.94 (dd, J = 8.9 Hz, 3.0 Hz, 1H, H4), 6.63 (d, J = 8.9 Hz, 1H, H6), 5.13 (br s, 2H, NH2), 3.87 (s, 3H, OMe), 3.76 (s, 3H, OMe);13C {1H} NMR (75 MHz, CDCl3) δ 168.4, 150.7, 145.1, 123.4, 118.4, 113.2, 110.9, 56.0, 51.7;To an ethyl acetate (14mL) solution of methyl 5-methoxy-2-nitrobenzoate (1.60g, 7.58 mmol), 10percent palladium-carbon (containing 50percent water) (320mg) was added and stirred under a hydrogen atmosphere of 0.25MPa at 20-25°C for 3 hours. After the reaction, palladium-carbon was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane/ethyl acetate = 10/1 - 5/1) to give methyl 2-amino-5-methoxybenzoate (1.29g, 94percent) Methyl 2-nitro-5- (methyloxy) benzoate (27.21 g, 0.129 mol) was added to a 1000 ml single-Soluble ethanol solution (absolute ethanol: water = 1: 1), Reducing iron powder (14.40 g, 0.258 mol) andAmmonium chloride (20.68 g, 0.387 mol), Reflux 13h.The reaction was complete, suction filtration, the filtrate was extracted with ethyl acetate, combined ethyl acetate layer, with anhydrousDried over sodium sulfate, The solvent was distilled off under reduced pressure to give 19.92 g of methyl 2-amino-5- (methoxy) benzoate, yield 85.3percent.2-amino-5-methoxybenzoic acid (250 mg, 1.496 mmol) was dissolved in MeOH(7478 tL). Thionyl chloride (327 tL, 4.49 mmol) was added and the reaction mixturewas heated to reflux for 3 days. The reaction mixture was concentrated in vacuo. Thecrude material was dissolved in EtOAc and washed with 1 N NaOH, then water, thenbrine, dried (Na2SO4), filtered, and concentrated in vacuo to give Intermediate I-20A (190mg, 1.049 mmol, 70.1percent) as a brown oil: ‘H NMR (400MHz, CHLOROFORM-d) 7.38(d, J3. 1 Hz, 1H), 6.98 (dd, J9.0, 3.1 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 5.43 (br. s., 2H), 3.90 (s, 3H), 3.79 (s, 3H); LC-MS: Method H, RT = 0.89 mm, MS (ESI) m/z: 182.1(M+H)Hydrogen chloride gas was bubbled through a solution of 2-amino-5- methoxybenzoic acid (5.0 g, 30 mmol) in MeOH (200 mL) for 30 minutes. The solution was heated at 60 °C overnight. The reaction was cooled and the solvent removed in vacuo. The residue was dissolved in water, basified with 5M NaOH and extracted twice with ether. The ether extracts were washed with 5M NaOH and water, dried (MgSOA mixture of the material so obtained, 10% palladium-on-charcoal catalyst (2.1 g), ethanol (200 ml) and ammonium formate (25.2 g) was stirred and heated to 70 C. for 2 hours. The mixture was filtered and the filtrate was evaporated. The residue was partitioned between methylene chloride and a dilute aqueous sodium bicarbonate solution. The organic layer was dried (MgSO4) and evaporated to give

Molecular Weight:181.19
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:181.07389321
Monoisotopic Mass:181.07389321
Topological Polar Surface Area:61.6
Heavy Atom Count:13
Complexity:184
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes