2-Amino-5-methoxybenzamide

Step 2 Step 2 To a suspension of 5-methoxy-2-nitrobenzamide (38.0 mmol) in methanol (150 mL), was added 10percent Pd-C (1.2 g) under an atmosphere of argon followed by addition of ammonium formate (18.0 g, 285.4 mmole). T resulting reaction mixture was refluxed for 2.5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Celite.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4.74g). The filtrate, was extracted with ethyl acetate (2x300 mL), dried (NaTo a suspension of 5-methoxy-2-nιtrobenzamide (38.0 mmol) in methanol ( 150 mL), was added 10percent Pd-C ( 1 2 g) under an atmosphere of argon followed by addition of ammonium formate ( 18 0 g, 285 4 mmole). T resulting reaction mixture was refluxed for 2 5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Cclitc.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4 74g) The filtrate, was extracted with ethyl acetate (2x300 mL), dried (NajSOα), filtered, concentrated in vacuo and combined with the previous solid The resulting solid was dried under vacuum to give 5-methoxy-2- aminobenzamide (4 74 g, 35 7 mmol, 94percent) HPLC retention time 3.16 mins.[0303] To a suspension of 5-methoxy-2-nitrobenzamide (38.0 mmol) in methanol(150 mL), was added 10percent Pd-C (1.2 g) under an atmosphere of argon followed by addition of ammonium formate (18.0 g, 285.4 mmole). T resulting reaction mixture was refluxed for 2.5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Celite.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4.74g). The filtrate, was extracted with ethyl acetate (2x300 mL), dried (Na(c) The 5-substituted-2-nitrobenzamides (2, 5-8) was dissolved in MeOH and hydrogenated over 10percent Pd/C for 1 to 2 hours. The catalyst was removed by filtration, and the solution was dried under vacuum to afford the 5-substituted-2-aminobenzamides 9-13 (9: 0.8 g, 86percent; 10: 0.9 g, 85percent; 11: 0.9 g, 85percent; 12: 0.9 g, 82percent; 13: 0.9 g, 82percent) as brown powdersExample 84 Accordingtoaliteratureprocedure, 3toasolutionof2-amino-5-methoxybenzoicacid(291mg, 1.74mmol, 1.0eq)indegassedDMF(3.50mL)wereaddedHOBt(339mg, 2.09 mmol, 1.2 eq.), EDCI.HCl (400 mg, 2.09 mmol, 1.2 eq.), N, N-diisopropylethylamine(606μL, 3.48mmol, 2.0eq), and7MNH3/MeOH(746μL, 5.22mmol, 3.0eq.).Thesolutionwasstirredatroomtemperaturefor24hoursthenpouredoverwaterandtheaqueouslayerextractedwithEtOAc(320mL), thecombinedorganiclayerswashedwithbrine(25mL), driedwithNa2SO4andconcentratedinvacuo.TheresiduewaspurifiedbyFCC(gradient 30percent EtOAc/hexanes to 60percent EtOAc/hexanes) to give 2-amino-5-methoxybenzamide(28.0mg, 0.168mmol, 10percent)asayellowamorphoussolid;mp:113–114°C.Intermediate A4: 2-amino-5-(methyloxy)benzamide; 6-methoxy-2/-/-3, 1-benzoxazine-2, 4(1H)-dione (3.Og, 16 mmol, Trans World Chemicals) was treated directly with 27percent aqueous ammonium hydroxide. After one hour the organic phase was diluted with ethyl acetate, washed twice with aqueous sodium bicarbonate and saturated aqueous sodium chloride, and dried over sodium sulfate. Filtration and removal of the residual solvent gave 2-amino-5-(methyloxy)benzamide as a white solid (1.42g, 53percent Yield);. 1 H NMR (400 MHz, DMSOdStep 2 To a solution of 5-methoxy-2-nitrobenzamide (9.70 g, 49.4 mmol) in methanol (250 mL) was added 10percent palladium carbon (2.00 g), and the mixture was stirred under hydrogen atmosphere (1 atm) at room temperature for 6 hr. The insoluble material was filtered off, and the filtrate was concentrated to give Step 2 To a solution (250 mL) of 5-methoxy-2-nitrobenzamide (9.70 g, 49.4 mmol) in MeOH was added 10percent Pd-C (2.00 g), and the mixture was stirred under a hydrogen atmosphere (1 atm) at room temperature for 6 hrs. Insoluble material was filtered off and the filtrate was concentrated to give To a suspension of 5-methoxy-2-nitrobenzamide (38.0 mmol) in methanol (150 mL), was added 10percent Pd-C (1.2 g) under an atmosphere of argon followed by addition of ammonium formate (18.0 g, 285.4 mmole). T resulting reaction mixture was refluxed for 2.5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Celite.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4.74g). The filtrate, was extracted with ethyl acetate (2x300 mL), dried (Na2SO4), filtered, concentrated in vacuo and combined with the previous solid. The resulting solid was dried under vacuum to give 5-methoxy-2- aminobenzamide (4.74 g, 35.7 mmol, 94percent). HPLC retention time 3.16 mins.To a suspension of 5-methoxy-2-niotatrobenzamide (38.0 mmol) in methanol ( 150 mL), was added 10percent Pd-C ( 1 2 g) under an atmosphere of argon followed by addition of ammonium formate ( 18 0 g, 285 4 mmole). T resulting reaction mixture was refluxed for 2 5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Cclitc.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4 74g) The filtrate, was extracted with ethyl acetate (2x300 mL), dried (NajSOalpha), filtered, concentrated in vacuo and combined with the previous solid The resulting solid was dried under vacuum to give 5-methoxy-2- aminobenzamide (4 74 g, 35 7 mmol, 94percent) HPLC retention time 3.16 mins.[0303] To a suspension of 5-methoxy-2-nitrobenzamide (38.0 mmol) in methanol(150 mL), was added 10percent Pd-C (1.2 g) under an atmosphere of argon followed by addition of ammonium formate (18.0 g, 285.4 mmole). T resulting reaction mixture was refluxed for 2.5 h, upon which, the mixture was allowed to cool to RT and was filtered through a pad of Celite.(R).. The filtrate was concentrated under reduced pressure and the residue was washed with water to give a solid (4.74g). The filtrate, was extracted with ethyl acetate (2x300 mL), dried (Na2SO4), filtered, concentrated in vacuo and combined with the previous solid. The resulting solid was dried under vacuum to give 5-methoxy-2- aminobenzamide (4.74 g, 35.7 mmol, 94percent). HPLC retention time 3.16 mins.(c) The 5-substituted-2-nitrobenzamides (2, 5-8) was dissolved in MeOH and hydrogenated over 10percent Pd/C for 1 to 2 hours. The catalyst was removed by filtration, and the solution was dried under vacuum to afford the 5-substituted-2-aminobenzamides 9-13 (9: 0.8 g, 86percent; 10: 0.9 g, 85percent; 11: 0.9 g, 85percent; 12: 0.9 g, 82percent; 13: 0.9 g, 82percent) as brown powdersGeneral procedure: To a magnetically stirred suspension of stannous chloride (0.038 mol) in concentrated HCl (37percent), 0.013 mol of 7a-c was added (15 ml) at a rate so that the temperature of the slurry was maintained below 5 °C (about 1 h). After addition was complete, the mixture was stirred for 24 h. The white slurry thus obtained was diluted with cold water (150 ml), and sodium hydroxide (40percent) was added until the tin salt dissolved. The solution was extracted with ethyl acetate (3 150 ml), and the extracts dried and evaporated in vacuo to obtain pure 2d, f, g.General procedure: To a magnetically stirred suspension of stannous chloride (0.038 mol) in concentrated HCl (37percent), 0.013 mol of 13a'c was added (15 mL) at a rate so that the temperature of the slurry was maintained below 5 °C (about 1 h). After addition was complete, the mixture was stirred for 24 h. The white slurry thus obtained was diluted with cold water (150 mL), and NaOH (40percent) was added until the tin salt dissolved. The solution was extracted with ethylacetate (3 150 mL), and the extracts dried and evaporated to obtain pure 15d, e, f.

Molecular Weight:166.18
XLogP3:0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:166.074227566
Monoisotopic Mass:166.074227566
Topological Polar Surface Area:78.3
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes