Benzamide, 2,3-diamino-

SYNTHESIS EXAMPLESNo. 1-1: 2-[chloro(difluoro)methyl]-1H-benzimidazole-4-carboxamide; 2-Amino-3-nitrobenzoic acid (3.00 g, 16.47 mmol) was dissolved in dimethoxyethane (15 ml), thionyl chloride was added (2.61 g, 21.91 mmol), and the mixture was stirred at 50° C. for 12 h. Subsequently, the reaction mixture was concentrated under reduced pressure, the solvent was removed and then toluene was added, and the mixture was concentrated again. Thereafter, aqueous saturated ammonia solution (40 ml) was initially charged in a round-bottom flask and cooled to 10° C., and the acid chloride (3.30 g, 16.45 mmol) from the first step, which had not been purified any further, was added dropwise while stirring vigorously. In the course of this, the temperature of the reaction mixture was kept below 40° C. After the end of the addition, the reaction mixture was stirred at 50° C. for one hour, then diluted with water and stirred at room temperature. By filtering off the orange precipitate which formed with suction, washing with water and drying, 2-amino-3-nitrobenzamide (2.60 g, 87percent) was obtained. 2-Amino-3-nitrobenzamide (2.60 g, 14.35 mmol) was then added in a metal vessel to palladium on carbon (water-moist catalyst, 10percent Pd, 0.05 equiv., 0.072 mmol) in methanol (80 ml). In a laboratory reactor, hydrogen was introduced into the metal vessel and the resulting reaction mixture was stirred at room temperature at a pressure of 2 bar for 5 h. After complete conversion, the catalyst was filtered off through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and the residue was extracted with water and ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude product did not need any further purification and contained 2, 3-diaminobenzamide (2.15 g, 98percent) in a purity of >95percent. 2, 3-Diaminobenzamide (200 mg, 1.32 mmol) was dissolved in chlorodifluoroacetic acid (3 ml) with vigorous stirring. The resulting reaction mixture was subsequently stirred under reflux for 3 h. After cooling to room temperature, NaHCO  2-Amino-3-nitrobenzoic acid (3.00 g, 16.47 mmol) was dissolved in dimethoxyethane (15 ml), thionyl chloride was added (2.61 g, 21.91 mmol), and the mixture was stirred at 50°C for 12 h. Subsequently, the reaction mixture was concentrated under reduced pressure, the solvent was removed and then toluene was added, and the mixture was concentrated again. Thereafter, aqueous saturated ammonia solution (40 ml) was initially charged in a round-bottom flask and cooled to 10°C, and the acid chloride (3.30 g, 16.45 mmol) from the first step, which had not been purified any further, was added dropwise while stirring vigorously. In the course of this, the temperature of the reaction mixture was kept below 40°C. After the end of the addition, the reaction mixture was stirred at 50°C for one hour, then diluted with water and stirred at room temperature. By filtering off the orange precipitate which formed with suction, washing with water and drying, 2-amino-3-nitrobenzamide (2.60 g, 87percent) was obtained. 2-Amino-3-nitrobenzamide (2.60 g, 14.35 mmol) was then added in a metal vessel to palladium on carbon (water-moist catalyst, 10percent Pd, 0.05 equiv., 0.072 mmol) in methanol (80 ml). In a laboratory reactor, hydrogen was introduced into the metal vessel and the resulting reaction mixture was stirred at room temperature at a pressure of 2 bar for 5 h. After complete conversion, the catalyst was filtered off through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and the residue was extracted with water and ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude product did not need any further purification and contained 2, 3-diaminobenzamide (2.15 g, 98percent) in a purity of > 95percent. 2, 3-Diaminobenzamide (200 mg, 1.32 mmol) was dissolved in chlorodifluoroacetic acid (3 ml) with vigorous stirring. The resulting reaction mixture was subsequently stirred under reflux for 3 h. After cooling to room temperature, NaHCOPd/C (200 mg) is added to a stirred mixture of 2-amino-3- nitrobenzamide (1.81 g, 10.0 mmoles) or 2-AMINO-3-NITRO- (N- substituted) -benzamide and ammonium-formiate (3.78 g, 0.06 mol) in methanol (40 mL) or some other appropriate solvent and the mixture is stirred at 40 °C for 2 hours. The mixture is then filtered through Cellite, washed with methanol (40 mL) or the used solvent, evaporated and the residue is purified by way of crystallyzation or flash column chromatography to give 2, 3-diaminobenzamide as a pale brown light sensitive solid (800 mg, 53 percent), MP 103-105 °C ; v max (CM-1) 3330, 3170, 1630, 1600, MS m/z (percent) : 151 (M+, 70), 134 (72), 106 (100) 79 (38). The same method can be used for 2, 3-DIAMINO- (N-SUBSTITU- ted) benzamidesSYNTHESIS EXAMPLESNo. 1-1: 2-[chloro(difluoro)methyl]-1H-benzimidazole-4-carboxamide; 2-Amino-3-nitrobenzoic acid (3.00 g, 16.47 mmol) was dissolved in dimethoxyethane (15 ml), thionyl chloride was added (2.61 g, 21.91 mmol), and the mixture was stirred at 50 C. for 12 h. Subsequently, the reaction mixture was concentrated under reduced pressure, the solvent was removed and then toluene was added, and the mixture was concentrated again. Thereafter, aqueous saturated ammonia solution (40 ml) was initially charged in a round-bottom flask and cooled to 10 C., and the acid chloride (3.30 g, 16.45 mmol) from the first step, which had not been purified any further, was added dropwise while stirring vigorously. In the course of this, the temperature of the reaction mixture was kept below 40 C. After the end of the addition, the reaction mixture was stirred at 50 C. for one hour, then diluted with water and stirred at room temperature. By filtering off the orange precipitate which formed with suction, washing with water and drying, 2-amino-3-nitrobenzamide (2.60 g, 87%) was obtained. 2-Amino-3-nitrobenzamide (2.60 g, 14.35 mmol) was then added in a metal vessel to palladium on carbon (water-moist catalyst, 10% Pd, 0.05 equiv., 0.072 mmol) in methanol (80 ml). In a laboratory reactor, hydrogen was introduced into the metal vessel and the resulting reaction mixture was stirred at room temperature at a pressure of 2 bar for 5 h. After complete conversion, the catalyst was filtered off through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and the residue was extracted with water and ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude product did not need any further purification and contained 2-Amino-3-nitrobenzoic acid (3.00 g, 16.47 mmol) was dissolved in dimethoxyethane (15 ml), thionyl chloride was added (2.61 g, 21.91 mmol), and the mixture was stirred at 50C for 12 h. Subsequently, the reaction mixture was concentrated under reduced pressure, the solvent was removed and then toluene was added, and the mixture was concentrated again. Thereafter, aqueous saturated ammonia solution (40 ml) was initially charged in a round-bottom flask and cooled to 10C, and the acid chloride (3.30 g, 16.45 mmol) from the first step, which had not been purified any further, was added dropwise while stirring vigorously. In the course of this, the temperature of the reaction mixture was kept below 40C. After the end of the addition, the reaction mixture was stirred at 50C for one hour, then diluted with water and stirred at room temperature. By filtering off the orange precipitate which formed with suction, washing with water and drying, 2-amino-3-nitrobenzamide (2.60 g, 87%) was obtained. 2-Amino-3-nitrobenzamide (2.60 g, 14.35 mmol) was then added in a metal vessel to palladium on carbon (water-moist catalyst, 10% Pd, 0.05 equiv., 0.072 mmol) in methanol (80 ml). In a laboratory reactor, hydrogen was introduced into the metal vessel and the resulting reaction mixture was stirred at room temperature at a pressure of 2 bar for 5 h. After complete conversion, the catalyst was filtered off through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and the residue was extracted with water and ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude product did not need any further purification and contained Add 2-amino-3-nitrobenzamide VI (10g, 55.20mmol) to a 1L reaction flask, add 500mL anhydrous methanol and stir to dissolve, slowly add 10% Pd/C (1g, dry), hydrogenation at 25 C reaction.TLC (dichloromethane: methanol = 20:1) The reaction of the starting material was monitored completely, the reaction was stopped, and palladium carbon was removed by suction filtration.Concentrated filtrate under reduced pressure, column chromatography(Dichloromethane: methanol = 200:1) Purified to give product (VII) 5.0 g, yield 60.0%.Add 2-amino-3-nitrobenzamide VI (10g, 55.20mmol) to a 1L reaction flask, add 500mL anhydrous methanol and stir to dissolve, slowly add 10% Pd/C (1g, dry), hydrogenation at 25 C reaction. TLC (dichloromethane: methanol = 20:1) was used to monitor the reaction of the starting material, the reaction was stopped, the palladium carbon was removed by suction filtration, and the filtrate was concentrated under reduced pressure.1) Purification, product (VII) 5.0 g, yield 60.0%.Pd/C (200 mg) is added to a stirred mixture of 2-amino-3- nitrobenzamide (1.81 g, 10.0 mmoles) or 2-AMINO-3-NITRO- (N- substituted) -benzamide and ammonium-formiate (3.78 g, 0.06 mol) in methanol (40 mL) or some other appropriate solvent and the mixture is stirred at 40 C for 2 hours. The mixture is then filtered through Cellite, washed with methanol (40 mL) or the used solvent, evaporated and the residue is purified by way of crystallyzation or flash column chromatography to give General procedure: The corresponding nitroaniline (1 eq.) was added to 50% aqueous ethanol (5 mL/g) at room temperature and heated to reflux. Sodium dithionite (10 eq.) was added portion-wise. The reaction was heated under reflux for 30 min. TLC confirmed consumption of starting material (100% ethyl acetate, UV). The cooled reaction mixture was extracted four times with ethyl acetate (4 × 10 mL/g) and the combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. The product was isolated as per specification.The mixture of 206 g (1.14 mol) of 6 and 20, 6 g of 10% Pd on charcoal in 824 ml of THF and 824 ml of methanol was hydrogenated with a total of 6 equivalents of hydrogen (130 I) at 20-480C over 24 h. The mixture was filtrated and the solvents were evaporated.

Molecular Weight:151.17
XLogP3:-0.3
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:151.074561919
Monoisotopic Mass:151.074561919
Topological Polar Surface Area:95.1
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes