2-Bromo-4-chlorobenzeneacetic acid

General procedure: To a magnetically stirred solution of 2-(2-bromophenyl)acetic acid7a (0.72g, 3.3 mmol) and 2-amino-3, 4-dimethylbenzoic acid 8a (0.5g, 3.0 mmol) in DMF was added powdered Cu (0.02g), Cu2O (0.02g) andK2CO3 (0.33g, 2.4 mmol) successively. The reaction mixture was heatedat 95 for 12 h. Upon removal of the solvents, the residue was trituratedwith 1 N NaOH solution. The whole mixture was filtered off andthe alkaline solution was acidified with conc.HCl, and then collectedthe precipitate. The dried residue was subjected to column purification(PE/EA 2:1) to furnish the desired compound. A solution of 2-((2-(carboxymethyl) phenyl) amino)-3, 4-dimethylbenzoic acid in Eaton'sreagent (P2O5 -CH3SO3H) (5 ml) at room temperature was heated to90 C for 1 h. After cooling to room temperature, the mixture was addedslowly to the saturated aqueous NaHCO3 solution. The crude 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione was accumulatedby filtration followed by purification with silica gel column chromatography.Finally, NaOH (0.1g) was added to a solution of 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione in EtOH (20 ml) and water (2 ml). The resulting mixture was refluxed overnight. Uponremoval of the solvents, the residue was dissolved with water. Then, thesolution was neutralized by conc.HCl. After filtering the mixture, thecrude was obtained and purified by silica gel column chromatographyto give 0.36g 2a as yellow solid in a yield of 43.8%. 1H NMR (400 MHz, DMSO-D6) delta (ppm): 13.14 (s, 1H), 9.50 (s, 1H), 8.19 (dd, J = 8.1, 1.3 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.69 (dd, J = 7.2, 1.5 Hz, 1H), 7.25 (m, J = 8.0, 7.2 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 4.12 (s, 2H), 2.50 (s, 3H), 2.45 (s, 3H). 13C NMR (101 MHz, DMSO-D6) delta (ppm):177.54 (s), 173.73 (s), 142.42 (s), 139.74 (s), 139.48 (s), 135.94 (s), 125.89 (s), 124.65 (s), 123.64 (s), 123.17 (s), 121.67 (s), 121.26 (s), 119.43 (s), 38.77 (s), 21.21 (s), 12.70 (s). HRMS (ESI) m/z [M+H] + calculated for C17H15NO3: 282.1130 found: 282.1124.General procedure: To a magnetically stirred solution of 2-(2-bromophenyl)acetic acid7a (0.72g, 3.3 mmol) and 2-amino-3, 4-dimethylbenzoic acid 8a (0.5g, 3.0 mmol) in DMF was added powdered Cu (0.02g), Cu2O (0.02g) andK2CO3 (0.33g, 2.4 mmol) successively. The reaction mixture was heatedat 95 for 12 h. Upon removal of the solvents, the residue was trituratedwith 1 N NaOH solution. The whole mixture was filtered off andthe alkaline solution was acidified with conc.HCl, and then collectedthe precipitate. The dried residue was subjected to column purification(PE/EA 2:1) to furnish the desired compound. A solution of 2-((2-(carboxymethyl) phenyl) amino)-3, 4-dimethylbenzoic acid in Eaton'sreagent (P2O5 -CH3SO3H) (5 ml) at room temperature was heated to90 C for 1 h. After cooling to room temperature, the mixture was addedslowly to the saturated aqueous NaHCO3 solution. The crude 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione was accumulatedby filtration followed by purification with silica gel column chromatography.Finally, NaOH (0.1g) was added to a solution of 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione in EtOH (20 ml) and water (2 ml). The resulting mixture was refluxed overnight. Uponremoval of the solvents, the residue was dissolved with water. Then, thesolution was neutralized by conc.HCl. After filtering the mixture, thecrude was obtained and purified by silica gel column chromatographyto give 0.36g 2a as yellow solid in a yield of 43.8%. 1H NMR (400 MHz, DMSO-D6) delta (ppm): 13.14 (s, 1H), 9.50 (s, 1H), 8.19 (dd, J = 8.1, 1.3 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.69 (dd, J = 7.2, 1.5 Hz, 1H), 7.25 (m, J = 8.0, 7.2 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 4.12 (s, 2H), 2.50 (s, 3H), 2.45 (s, 3H). 13C NMR (101 MHz, DMSO-D6) delta (ppm):177.54 (s), 173.73 (s), 142.42 (s), 139.74 (s), 139.48 (s), 135.94 (s), 125.89 (s), 124.65 (s), 123.64 (s), 123.17 (s), 121.67 (s), 121.26 (s), 119.43 (s), 38.77 (s), 21.21 (s), 12.70 (s). HRMS (ESI) m/z [M+H] + calculated for C17H15NO3: 282.1130 found: 282.1124.General procedure: To a magnetically stirred solution of 2-(2-bromophenyl)acetic acid7a (0.72g, 3.3 mmol) and 2-amino-3, 4-dimethylbenzoic acid 8a (0.5g, 3.0 mmol) in DMF was added powdered Cu (0.02g), Cu2O (0.02g) andK2CO3 (0.33g, 2.4 mmol) successively. The reaction mixture was heatedat 95 for 12 h. Upon removal of the solvents, the residue was trituratedwith 1 N NaOH solution. The whole mixture was filtered off andthe alkaline solution was acidified with conc.HCl, and then collectedthe precipitate. The dried residue was subjected to column purification(PE/EA 2:1) to furnish the desired compound. A solution of 2-((2-(carboxymethyl) phenyl) amino)-3, 4-dimethylbenzoic acid in Eaton'sreagent (P2O5 -CH3SO3H) (5 ml) at room temperature was heated to90 C for 1 h. After cooling to room temperature, the mixture was addedslowly to the saturated aqueous NaHCO3 solution. The crude 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione was accumulatedby filtration followed by purification with silica gel column chromatography.Finally, NaOH (0.1g) was added to a solution of 9, 10-dimethyl-6H-pyrrolo[3, 2, 1-de] acridine-1, 6(2H)-dione in EtOH (20 ml) and water (2 ml). The resulting mixture was refluxed overnight. Uponremoval of the solvents, the residue was dissolved with water. Then, thesolution was neutralized by conc.HCl. After filtering the mixture, thecrude was obtained and purified by silica gel column chromatographyto give 0.36g 2a as yellow solid in a yield of 43.8%. 1H NMR (400 MHz, DMSO-D6) delta (ppm): 13.14 (s, 1H), 9.50 (s, 1H), 8.19 (dd, J = 8.1, 1.3 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.69 (dd, J = 7.2, 1.5 Hz, 1H), 7.25 (m, J = 8.0, 7.2 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 4.12 (s, 2H), 2.50 (s, 3H), 2.45 (s, 3H). 13C NMR (101 MHz, DMSO-D6) delta (ppm):177.54 (s), 173.73 (s), 142.42 (s), 139.74 (s), 139.48 (s), 135.94 (s), 125.89 (s), 124.65 (s), 123.64 (s), 123.17 (s), 121.67 (s), 121.26 (s), 119.43 (s), 38.77 (s), 21.21 (s), 12.70 (s). HRMS (ESI) m/z [M+H] + calculated for C17H15NO3: 282.1130 found: 282.1124.

Molecular Weight:249.49
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:247.92397
Monoisotopic Mass:247.92397
Topological Polar Surface Area:37.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes