4-CHLORO-7-BROMOINDOLE

Preparation of 4-chloro-1H-indole-7-carboxylic acid; 1.19 g (5 mmol) of 2-bromo-5-chloro-nitrobenzene were dissolved in 50 ml THF. At a temperature of -45° C. 15 ml of a 1M vinyl magnesium bromide solution in THF were added under nitrogen in such a way that the temperature did not exceed -40° C. After complete addition the dark solution was stirred for 30 min at -40° C. The reaction mixture was quenched with 10 ml aqueous saturated ammonium chloride solution and extracted twice with diethyl ether. The combined organic layers were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (100 g silica gel; heptane/EtOAc 19:1) to yield 562 mg (49percent) of 7-bromo-4-chloro-1H-indole as an orange oil. MS (EI) 229.0 (80), 231.0 (100), 233.0 (30) (M)To a stirred solution of l-bromo-4chloro-2-nitrobenzene (1.3g, 5.49mmol) in THF(28ml) was added vinylmagnesium bromide (1M in THF, 16.5ml, 123mmol) at -45°C and the reaction mixture was stirred at the same temperature for lhour. Then the reaction mixture was quenched with saturated NH4CI (20ml). The volatile components were evaporated under reduced pressure and HPreparation 44 Under a nitrogen gas, 1-bromo-4-chloro- 2-nitrobenzene (25g, 0.107mol) was dissolved in THF (250mL), added dropwise vinylmagnesium bromide (1M in THF, 321mL , 0.321mol) in -40 degree celcius , and then slowly was stirred at -40 degree celcius for 1 hour. Since, NHExample S65; Preparation of 4-chloro-1H-indole-7-carboxylic acid; 1.19 g (5 mmol) of 2-bromo-5-chloro-nitrobenzene were dissolved in 50 ml THF. At a temperature of -45 C. 15 ml of a 1M vinyl magnesium bromide solution in THF were added under nitrogen in such a way that the temperature did not exceed -40 C. After complete addition the dark solution was stirred for 30 min at -40 C. The reaction mixture was quenched with 10 ml aqueous saturated ammonium chloride solution and extracted twice with diethyl ether. The combined organic layers were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (100 g silica gel; heptane/EtOAc 19:1) to yield 562 mg (49%) of To a stirred solution of l-bromo-4chloro-2-nitrobenzene (1.3g, 5.49mmol) in THF(28ml) was added vinylmagnesium bromide (1M in THF, 16.5ml, 123mmol) at -45C and the reaction mixture was stirred at the same temperature for lhour. Then the reaction mixture was quenched with saturated NH4CI (20ml). The volatile components were evaporated under reduced pressure and H20 (30ml) was added to the resulting residue. The crude was extracted with DCM (2x 15ml) and the organic layer was washed with brine (50ml) dried over Na2S04 and concentrated in vacuo. The residue was purified by flash - - chromatography using AcOEt/Heptane (1/19) to give the title compound as a yellow oil (0.6g, 47%) NMR (400MHZ, CDC13): 8.35 (s, 1H, br), 7.22 (t, 1H, J= 2.8Hz), 7.17 (d, 1H, J= 8Hz) 6.94 (d, J=8Hz, 1H), 6.66 (t, 1H, J= 2.8Hz) 13C NMR (100 MHz, CDCI3): 135.0, 127.5, 125.6, 125.2, 124.7, 120.7, 102.8Preparation 44 7-Bromo-4-chloro-1H-indole To a solution of 1-bromo-4-chloro-2-nitrobenzene (932 mg, 3.95 mmol) in tetrahydrofuran (10 mL), vinylmagnesium bromide (0.7 M in tetrahydrofuran) (12 mmol) in tetrahydrofuran (15 mL) was added drop wise at -40 C. After 1 h the reaction mixture was poured into saturated NH4Cl. The resulting organic layer was concentrated. The resulting residue was purified using a Teledyne ISCO chromatography system with a gradient eluent system of 2% ethyl acetate in hexane to yield the title compound (400 mg, 44%): 1H NMR (300 MHz, CDCl3) delta 6.73 (t, J=2.8 Hz, 1H), 7.02 (d, J=8.1 Hz, 1H), 7.19-7.39 (m, 2H), 8.43 (s, 1H).Under a nitrogen gas, 1-bromo-4-chloro- 2-nitrobenzene (25g, 0.107mol) was dissolved in THF (250mL), added dropwise vinylmagnesium bromide (1M in THF, 321mL , 0.321mol) in -40 degree celcius , and then slowly was stirred at -40 degree celcius for 1 hour. Since, NH4After completion of the reaction with Cl aqueous solution was raised to room temperature.Then, ethyl acetate and the organic layer was extracted with, MgSO4to remove water from the organic layer to the next, filtered and concentrated and purified by column chromatography with 7-Bromo-4-chloro-lH-indole was prepared from l-bromo-4-chloro-2-nitrobenzene and vinylmagnesium bromide using Bartoli indole synthesis condition (Tetrahedron Letters, 1989, Vol. 30, 2129-2132).Example 17, Step aTo a stirred solution of 1 -bromo-4-chloro-2-nitrobenzene (10 g, 42.3 mmol) in THF (125 mL) was added vinylmagnesium bromide (1M in THF, 127 mL, 127 mmol) at -78 C and the reaction mixture was stirred at the same temperature for 30 minutes. Then the reaction mixture was quenched with saturated NH4C1 (60 mL). The volatile components were evaporated under reduced pressure and H20 (100 mL) was added to the resulting residue. The crude was extracted with DCM (2 x 50 mL), and the organic layer was washed with brine (50 mL), dried over Na2S04 and concentrated in vacuo. The residue was purified by flash chromatography (Silica gel 230-400, 1.3 % EtO Ac/petroleum ether) to yield 17a (4.5 g) as brown oil. LC/MS (Condition 15): Rt = 2.01 min. 'H NMR (DMSO-d6, delta = 2.50 ppm, 400 MHz): delta 11.72 (br s, 1H), 7.52 (t, J = 2.8, 1H), 7.32 (d, J = 8.0, 1H), 7.05 (d, J = 8.0, 1H), 6.61-6.59 (m, 1H). LC/MS: Anal. Calcd. for [M-H] C8H4BrClN: 227.93; found 228.0.under nitrogen gas,

Molecular Weight:230.49
XLogP3:3.4
Hydrogen Bond Donor Count:1
Exact Mass:228.92939
Monoisotopic Mass:228.92939
Topological Polar Surface Area:15.8
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes