6-Chloro-1H-indole-3-carboxylic acid

b) 1- (6-chloro-1 H-indol-3-yl) -2, 2, 2-trifluoroethan-1-one (9.0 g)4 M aqueous potassium hydroxide solution (40 mL) was added, And the mixture was stirred under heating reflux for 3.5 hours. After cooling the reaction solution to 0 ° C. with ice, Concentrated hydrochloric acid was added to acidify, the precipitated solid was filtered with hexane and ethyl acetate, By washing, 6-Chloro-lH-indole-3-carboxylic acid5.4 g (yield 84percent) was obtained.1-(6-Chloro-1H-indol-3-yl)-2, 2, 2-trifluoroethanone (he) (743 mg, 3.0 mmol) was suspended in 10 mL of a 4M aqueous solution of sodium hydroxide. The resulting mixture was stirred at reflux during 1 hour. The solution was extracted with diethyl ether (2x25 mL) and then aqueous phase was acidified with an aqueous solution of 5M HCl to pH 1. The precipitate was filtered off, washed with water and dried in the presence of P2O5. Pure 6-chloroindolic acid (2e) (475 mg, 2.43 mmol) was obtained as a beige solid. Yield: 81percent. 1H NMR (300 MHz, (CD3)2CO): δ = 7.20 (dd, J = 1.8 and 8.6 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 8.01-8.13 (m, 2H), 11.02 (br s, 1H), 11.02 (br s, 1H, NH) ppm. 13C NMR (75.5 MHz, (CD3)2CO): δ = 110.6 (C), 113.7 (CH), 123.6 (CH), 124.1 (CH), 125.4 (C), 128.2 (C), 134.8 (CH), 136.9 (C), 167.0 (CO) ppm.Its synthesis from 1-(6-chloro-1H-indol-3-yl)-2, 2, 2-trifluoroethanone (he) was described in the following patents: C. Bissantz et al, PCT Int. AppL, 2007009906, 25 Jan 2007 (synthesis from 6-chloroindole according to J. Med. Chem. 1991, 34, 140); C. Bissantz et al, U.S. Pat. AppL PubL, 20080161332, 03 Jul 2008. l-(6-Chloro-lH-indol-3-yl)-2, 2, 2-trifluoroethanone (he) (743 mg, 3.0 mmol) was suspended in 10 mL of a 4M aqueous solution of sodium hydroxide. The resulting mixture was stirred at reflux during 1 hour. The solution was extracted with diethyl ether (2x25 mL) and then aqueous phase was acidified with an aqueous solution of 5M HCl to pH 1. The precipitate was filtered off, washed with water and dried in the presence of PA mixture of 1.3 g (5.3 mmol) 1-(6-chloro-1H-indol-3-yl)-2, 2, 2-trifluoro-ethanone 26.5 ml of a 4 M aqueous solution of sodium hydroxide was heated at reflux for 4.5 h. b) 6-Chloro-1H-indole-3-carboxylic acid (1.0 g)Of DMF (30 mL)60% sodium hydride (450 mg) was added to the solution, After stirring at room temperature for 30 minutes, 2-Chloropyrimidine (644 mg) was added, And the mixture was stirred at 120 C. for 18 hours.After cooling the reaction solution to room temperature, water (100 mL) and ethyl acetate (100 mL) were added and the mixture was extracted with ethyl acetate. The obtained aqueous layer was made acidic with concentrated hydrochloric acid, After stirring at room temperature for 30 minutes, the obtained solid was collected by filtration, By washing with water, 1.2 g (yield 89%) of 6-chloro-1- (pyrimidin-2-yl) -1H-indole-3-carboxylic acid was obtained6-chloro-lH-indole-3-carboxylic acid (243 mg), 1- (4-methoxyphenyl) piperazine (238 mg), EDC (309 mg), HOBt (218 mg)And triethylamine (0.23 mL)Was dissolved in dichloromethane (10 mL)And the mixture was stirred at room temperature for 19 hours. Water was added to the reaction solution, It was extracted with dichloromethane, And washed with saturated brine. The organic layer was dried over sodium sulfate, By distilling off the solvent under reduced pressure, 6-Chloro-3- [4- (4-methoxyphenyl) piperazine-1-carbonyl] -1 H-indole470 mg as a crude product.

Molecular Weight:195.60
XLogP3:2.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:195.0087061
Monoisotopic Mass:195.0087061
Topological Polar Surface Area:53.1
Heavy Atom Count:13
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes