5-bromo-1-methyl-1H-indole-3-carboxylicacid

General procedure: In a 50 mL autoclave equipped with a glass inner tube and a magnetic stirring bar were charged indole 1a (d 1.05; 125 mL, 1.00 mmol), Me2AlCl (1.0 M solution in hexane; 1.0 mL, 1.0 mmol), toluene (1.0 mL) under nitrogen atmosphere, and the apparatus was purged with CO2 by repeated pressurization and subsequent expansion, the final pressure being adjusted to 3.0 MPa. After the mixture was stirred at 80 °C for 3 h, the reactor was allowed to cool to room temperature and depressurized. The reaction mixture was quenched with 2 M HCl and the aqueous layer was extracted with ethyl acetate. The combined organic layer was extracted with 0.5M Na2CO3 and the extract was acidified by the addition of concentrated HCl to liberate the free carboxylic acid, which was extracted with ethyl acetate. The extract was dried over MgSO4 and evaporated to leave a residue, which was purified by column chromatography with chloroform-ethyl acetate (1:1) as an eluent to give acid 2a as crystals (168 mg, 96percent). The carboxylation of other indoles was conducted by a similar procedure. The crude product was routinely purified by column chromatography using chloroform-ethyl acetate (1:1) or chloroform-ethyl acetate (1:1) containing 1percent (v/v) of acetic acid as an eluent. See Tables 1 and 2 for the reaction conditions and product yields.A flask was charged with compound (hm) (1.53 g, 5.03 mmol) and a 4M aqueous solution of sodium hydroxide (40 mL). This mixture was refluxed for 2h30. Methanol (10 mL) was added to the mixture which was refluxed overnight, then carefully acidified with 6M HCl. During this acidification, the carboxylic acid precipitated. The resulting suspension was filtered. The solid was washed with water and dissolved in a mixture of ethyl acetate/methanol (about 9/1). The organic layer was dried over anhydrous MgSO4 and evaporated under vacuum. The desired product (2m) (560 mg, 2.20 mmol) was obtained as a beige solid. Yield: 44percent. 1H NMR (300 MHz, DMSO-d6): δ = 3.84 (s, 3H, CH3), 7.38 (dd, J = 2.1 and 8.7 Hz, 1H, CH), 7.52 (d, J= 8.7 Hz, 1H, CH), 8.08 (s, 1H, CH), 8.13 (d, J= 2.1 Hz, 1H, CH), 12.13 (br s, 1H, OH) ppm. 13C NMR (75.5 MHz, DMSO-d6): δ = 33.1 (CH3), 105.7 (C), 112.8 (CH), 114.2 (C), 122.7 (CH), 124.6 (CH), 128.0 (C), 135.7 (C), 137.1 (CH), 165.1 (C) ppm.A flask was charged with compound (hm) (1.53 g, 5.03 mmol) and a 4M aqueous solution of sodium hydroxide (40 mL). This mixture was refluxed for 2h30. Methanol (10 mL) was added to the mixture which was refluxed overnight, then carefully acidified with 6M HCl. During this acidification, the carboxylic acid precipitated. The resulting suspension was filtered. The solid was washed with water and dissolved in a mixture of ethyl acetate/methanol (about 9/1). The organic layer was dried over anhydrous MgS0General procedure: 5-Bromo-1-methyl-indolyl-3-carbohydrazide or 1-methylindolyl-3-carbohydrazide (500 mg, 1.0 eq.) was added to differentindole-3-carboxylic acids (1.87 mmol, 1.0 eq.). To this reactionmixture, 12 vol of polyphosphoric acid was added and heated at90oc over a period of 3.5 he4 h. The reaction mixture was cooled toroom temperature and followed by addition of ice. The PH of theabove reaction mixture was brought to neutral by using sodiumbicarbonate solution. The solid obtained was separated and dried.The crude compoundwas purified by column chromatography withDCM solvent. The solvent was concentrated with rotary undercooling conditions when yellow colored solid was formed. It waswashed with n-hexane and ether solvent to remove non-polar andsemi-polar impurities, which yielded the pure compound in yellowcolor.General procedure: In a 50 mL autoclave equipped with a glass inner tube and a magnetic stirring bar were charged indole 1a (d 1.05; 125 mL, 1.00 mmol), Me2AlCl (1.0 M solution in hexane; 1.0 mL, 1.0 mmol), toluene (1.0 mL) under nitrogen atmosphere, and the apparatus was purged with CO2 by repeated pressurization and subsequent expansion, the final pressure being adjusted to 3.0 MPa. After the mixture was stirred at 80 C for 3 h, the reactor was allowed to cool to room temperature and depressurized. The reaction mixture was quenched with 2 M HCl and the aqueous layer was extracted with ethyl acetate. The combined organic layer was extracted with 0.5M Na2CO3 and the extract was acidified by the addition of concentrated HCl to liberate the free carboxylic acid, which was extracted with ethyl acetate. The extract was dried over MgSO4 and evaporated to leave a residue, which was purified by column chromatography with chloroform-ethyl acetate (1:1) as an eluent to give acid 2a as crystals (168 mg, 96%). The carboxylation of other indoles was conducted by a similar procedure. The crude product was routinely purified by column chromatography using chloroform-ethyl acetate (1:1) or chloroform-ethyl acetate (1:1) containing 1% (v/v) of acetic acid as an eluent. See Tables 1 and 2 for the reaction conditions and product yields.

Molecular Weight:254.08
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:252.97384
Monoisotopic Mass:252.97384
Topological Polar Surface Area:42.2
Heavy Atom Count:14
Complexity:246
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes