5-Bromo-1H-indole-7-carboxylic acid

Methyl 5-bromo-1 H-indole-7-carboxylate (5 g, 19.7 mmol) was dissolved in methanol (200 mL) and a solution of lithium hydroxide (0.99 g, 41 mmol) in water (10 mL) was added. The mixture was heated at reflux for 50 hours. The methanol was removed in vacuo and the residue diluted with aqueous hydrochloric acid (2 M). The resulting precipitate was filtered off and dried in a heated vacuum pistol to give 4.7 g (99percent) of the title compound as a beige solid.1 H NMR (400 MHz, DMSO-D6) δ ppm 6.54 (dd, J=2.0, 3.2 Hz, 1 H) 7.42 (t, J=2.8 Hz, 1 H) 7.77 (d, J=2 Hz, 1 H) 8.03 (d, J=1.8 Hz, 1 H) 11.27 (s, 1 H) 13.1-13.7 (bs, 1 H) MS m/z 238/240 (1 :1 ratio) (M-1 ) Rt 3.41 min.Intermediate 9:5-Bromo-1 H-indole-7-carboxylic acid.Methyl 5-bromo-1 H-indole-7-carboxylate (5 g, 19.7 mmol) was dissolved in methanol (200 ml.) and a solution of lithium hydroxide (0.99 g, 41 mmol) in water (10 ml.) was added.The mixture was heated at reflux for 50 hours. The methanol was removed in vacuo and the residue diluted with aqueous hydrochloric acid (2 M). The resulting precipitate was filtered off and dried in a heated vacuum pistol to give 4.7 g (99percent) of the title compound as a beige solid.1 H NMR (400 MHz, DMSO-d6) δ ppm 6.54 (dd, J=2.0, 3.2 Hz, 1 H) 7.42 (t, J=2.8 Hz, 1 H)7.77 (d, J=2 Hz, 1 H) 8.03 (d, J=1.8 Hz, 1 H) 11.27 (s, 1 H) 13.1-13.7 (bs, 1 H) MS m/z238/240 (1 :1 ratio) (M-1 ) Rt 3.41 min.409 mg of 5-bromo-1H-indole-7-carboxylic acid methyl ester (1.61 mmol) were suspended in a mixture of 1.6 ml 2N NaOH and 1.6 ml ethanol and stirred at 40° C. for 2 h. After cooling down, the mixture was treated with 2N aqueous HCl, and extracted twice with EtOAc. The organic phase was the washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo, leading to 353 mg of 5-bromo-1H-indole-7-carboxylic acid as a light brown solid (85percent). MS (ISP) 237.9 (M-H)463.5 mg of methyl 5-bromoanthranilate was placed in an argon atmosphere and dissolved in 2 mL of acetic acid. 499.5 mg of N-iodosuccinimide was added thereto, and the mixture was stirred at room temperature for 17 hours. The reaction solution was added dropwise to a saturated aqueous sodium hydrogen carbonate solution (5 mL) to neutralize acetic acid. This was extracted with ethyl acetate, and the ethyl acetate phase obtained was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and ethyl acetate was distilled off under reduced pressure.The obtained material was placed in an argon atmosphere and dissolved in 6.6 mL of triethylamine. 74.2 mg of bis (triphenylphosphine) palladium (II) dichloride, 22.3 mg of copper (I) iodide and 0.34 mL of trimethylsilylacetylene were added thereto, and the mixture was stirred at room temperature for 90 minutes. The reaction solution was diluted with dichloromethane, washed sequentially with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.The obtained substance dissolved in 9 mL of N-methyl-2-pyrrolidone was added dropwise to a mother liquor in which 512.3 mg of potassium tert-butoxide was changed to 0 ° C. under an argon atmosphere and 7 mL of N-methyl-2-pyrrolidone was added , Stirred for 1 hour, and then stirred at room temperature for 90 minutes. The reaction solution was again brought to 0 ° C., 32 mL of water was added, and the temperature was returned to room temperature. The diethyl ether phase extracted with diethyl ether was washed with water, saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, And the solvent was distilled off. The residue was dissolved in methanol, the insoluble matter was removed by filtration, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography using 10percent ethyl acetate / hexane as a developing solvent, and the solvent was distilled off .62.5 mg of the obtained substance was placed under an argon atmosphere, 2 N sodium hydroxide 2.4 mL and 2.4 mL ethanol were added and the temperature was adjusted to 40 ° C. and stirred for 2 hours. The reaction solution was brought to room temperature, the pH was made acidic using 3 N hydrochloric acid, sodium chloride was added until saturation, and the ethyl acetate phase eluted with ethyl acetate was dried with anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, it was suspended in diethyl ether, the brown solids in the insoluble matter was removed, and the remaining insoluble matter was washed with warm hexane. The solvent was distilled off, dissolved in ethyl acetate, activated charcoal was added to adsorb impurities, and the activated carbon was removed by filtration. The residue obtained by distilling off the solvent was dissolved in diethyl ether, the insoluble matter was removed by filtration, and the solvent was distilled off. As a result, 54.2 mg (yield 11.3percent) of a compound was obtained.

Molecular Weight:240.05
XLogP3:2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:238.95819
Monoisotopic Mass:238.95819
Topological Polar Surface Area:53.1
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes