2-AMINO-4-METHOXYCARBONYL BENZOIC ACID

Preparative Example 12Step 12-Amino-4-(methoxycarbonyl)benzoic Acid.12BA suspension of 4-(methoxycarbonyl)-2-nitrobenzoic acid (12A) (10.0 g, 44.4 mmol), and 5percent Pd/C (4.0 g) in 1 :1 MeOH/HExample 232: 3-(3-Chlorobenzo[b1thiophene-2-carboxamido)-4-cvclohexylcarbamoyl)- benzoic acidMethod 23A mixture of 2-amino-terephthalic acid (10.0 g, 55.1 mmol), 96percent sulfuric acid (10 mL) and MeOH (100 mL) was stirred at 60° for 7 h, then concentrated to half its volume, poured into ice and cautiously brought to pH 8 with about 20 g of solid sodium carbonate. The solution was washed with DCM (3 x 40 mL), then cautiously acidified to pH 2 with cone. HCI. The precipitate was collected by filtration, washed repeatedly with water and dried under vacuum at 40°C overnight. 2-Amino-terephthalic acid 4-methyl ester was obtained as a yellow solid (8.56 g, 80percent). To a suspension of this ester (2.0 g, 10.3 mmol) in DCM (65 mL), triethylamine (1.78 mL, 12.8 mmol) was added; after dissolution, 3-chloro- benzo[b]thiophene-2-carbonyl chloride (1.97 g, 8.55 mmol) was added and the mixture was stirred over 3 days at room temperature. The mixture was evaporated under vacuum and the residue was crystallized from about 50 mL of ethyl acetate, then washed with fresh ethyl acetate. 2-(3-Chloro-benzo[b]thiophene-2-carboxamido)terephthalic acid 4- methyl ester was obtained as a white solid (2.91 g, 73percent). A mixture of this compound (200 mg, 0.514 mmol), oxalyl chloride (0.052 mL, 0.617 mmol), DCM (5 mL) and 2 drops of DMF was refluxed for 1 h, then evaporated to dryness. The residue was mixed with cyclohexylamine (102 mg, 1.02 mmol) in DMF (5 mL) and the resulting solution was stirred for 1.5 h at room temperature. The solution was diluted with DCM (5 mL) and washed with diluted HCI, dried over sodium sulfate, filtered and evaporated under vacuum. The white solid residue was mixed with potassium carbonate (426 mg, 3.1 mmol), water (2 mL) and methanol (6 mL) and stirred at 90°C for 5 h. The clear solution thus formed was acidified with cone. HCI and stirring was continued for 1 h at room temperature, then the white precipitate was collected by suction filtration and washed repeatedly with water to obtain the title compound (93 mg, 40percent overall) as a white solid, mp > 200°C.

Molecular Weight:195.17
XLogP3:1.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:195.05315777
Monoisotopic Mass:195.05315777
Topological Polar Surface Area:89.6
Heavy Atom Count:14
Complexity:241
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes