1H-Indole, 4-broMo-6-(trifluoroMethyl)-

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-6-(trifluoromethyl)-1H-indole (300 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (422 mg), tetrakis(triphenylphosphine)palladium(0) (131 mg) and potassium carbonate (314 mg) in DME/water (3/0.5 mL) was stirred with microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (5 mL), 1N hydrochloric acid (2 mL) was added thereto, and the mixture was stirred overnight at room temperature. To the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (174 mg). extracted with ethyl acetate The extract was washed with water and saturated brine dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was dissolved in THF (5 mL) 1N hydrochloric acid (2 mL) was added the mixture was stirred overnight at room temperature To the reaction mixture was added saturated aqueous sodium bicarbonate solution the mixture was extracted with ethyl acetate The extract was washed with water and saturated brine dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-6-(trifluoromethyl)-1H-indole (300 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (422 mg), tetrakis(triphenylphosphine)palladium(0) (131 mg) and potassium carbonate (314 mg) in DME/water (3/0.5 mL) was stirred with microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (5 mL), 1N hydrochloric acid (2 mL) was added thereto, and the mixture was stirred overnight at room temperature. To the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (174 mg). extracted with ethyl acetate The extract was washed with water and saturated brine dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was dissolved in THF (5 mL) 1N hydrochloric acid (2 mL) was added the mixture was stirred overnight at room temperature To the reaction mixture was added saturated aqueous sodium bicarbonate solution the mixture was extracted with ethyl acetate The extract was washed with water and saturated brine dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of potassium tert-butoxide (1.33 g) in NMP (30 mL) was added a solution of 3-bromo-2-ethynyl-5-(trifluoromethyl)aniline (1.56 g) in NMP (5 mL) at 0° C., and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous ammonium chloride solution, water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (1.08 g). washed with saturated aqueous ammonium chloride solution, water and saturated brine dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromo-6-(trifluoromethyl)-1H-indole (5.23 g, 19.81 mmol) in tetrahydrofuran (20 ml) was cooled to −78 ° C. and treated slowly with n-butyllithium (1.6 M solution in hexanes, 39.6 ml, 63.4 mmol). The solution was stirred for 15 min at −78 ° C., and then treated with dimethylformamide (7.67 ml, 99 mmol), and stirred for 30 minutes more, allowing the reaction to warm to ambient temperature. The resulting solution was poured into brine and extracted with ethyl acetate. The pooled organics were dried over sodium sulfate and concentrated to give an amber oil. Column chromatography (ethyl acetate/hexanes gradient elution) afforded 1.17 g, (32%). 1H-NMR (CDCl3, 500 MHz) δ ppm 10.28 (s, 1H), 8.72 (br s, 1H), 7.93 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H). Mass spec.: 214.14 (MH)+. stirred for 30 minutes more the reaction to warm to ambient temperature extracted with ethyl acetate The pooled organics were dried over sodium sulfate concentrated to give an amber oil Column chromatography (ethyl acetate/hexanes gradient elution) afforded 1.17 g, (32%)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-bromo-6-(trifluoromethyl)-1H-indole (5.23 g, 19.81 mmol) in tetrahydrofuran (20 ml) was cooled to −78 ° C. and treated slowly with n-butyllithium (1.6 M solution in hexanes, 39.6 ml, 63.4 mmol). The solution was stirred for 15 min at −78 ° C., and then treated with dimethylformamide (7.67 ml, 99 mmol), and stirred for 30 minutes more, allowing the reaction to warm to ambient temperature. The resulting solution was poured into brine and extracted with ethyl acetate. The pooled organics were dried over sodium sulfate and concentrated to give an amber oil. Column chromatography (ethyl acetate/hexanes gradient elution) afforded 1.17 g, (32%). 1H-NMR (CDCl3, 500 MHz) δ ppm 10.28 (s, 1H), 8.72 (br s, 1H), 7.93 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H). Mass spec.: 214.14 (MH)+. stirred for 30 minutes more the reaction to warm to ambient temperature extracted with ethyl acetate The pooled organics were dried over sodium sulfate concentrated to give an amber oil Column chromatography (ethyl acetate/hexanes gradient elution) afforded 1.17 g, (32%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromo-2-ethynyl-5-(trifluoromethyl)aniline (7.54 g, 28.6 mmol) in N-methylpyrollidinone (50 mL) was added dropwise to a 0° C. solution of potassium tert-butoxide (6.41 g, 57.1 mmol) in N-methylpyrollidinone (200 mL). The reaction was stirred at ambient temperature for 4 h. The reaction was poured into brine (500 mL) and extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with brine (100 mL), dried with magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with a gradient of 10% to 25% ethyl acetate/hexanes to give 7.16 g (95%) as a brown oil. 1H-NMR (CDCl3, 400 MHz) δ 8.54 (bs, 1H), 7.63 (s, 1H), 7.53 (s, 1H), 7.40 (t, J=2.8 Hz, 1H), 6.66 (t, J=2.8 Hz, 1H); LC/MS (HPLC method 4): tR=3.280 min, 264.12(MH)+. extracted with ethyl acetate (4×50 mL) The combined organic layers were washed with brine (100 mL) dried with magnesium sulfate evaporated The residue was purified by chromatography on silica gel with a gradient of 10% to 25% ethyl acetate/hexanes to give 7.16 g (95%) as a brown oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min. 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6 H), 4.66-4.79 (m, 1 H), 6.65 (d, J=3.03 Hz, 1 H), 7.27-7.31 (m, 1 H), 7.45 (d, J=3.03 Hz, 1 H), 7.54 (s, 1 H), 7.63 (s, 1 H). MS: (M+H)+=306.2. the mixture was stirred overnight The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min. 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6H), 4.66-4.79 (m, 1H), 6.65 (d, J=3.03 Hz, 1H), 7.27-7.31 (m, 1H), 7.45 (d, J=3.03 Hz, 1H), 7.54 (s, 1H), 7.63 (s, 1H). MS: (M+H)+=306.2. the mixture was stirred overnight The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6H), 4.66-4.79 (m, 1H), 6.65 (d, J=3.03 Hz, 1H), 7.27-7.31 (m, 1H), 7.45 (d, J=3.03 Hz, 1H), 7.54 (s, 1H), 7.63 (s, 1H). MS: (M+H)+=306.2. was added The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min. 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6H), 4.66-4.79 (m, 1H), 6.65 (d, J=3.03 Hz, 1H), 7.27-7.31 (m, 1H), 7.45 (d, J=3.03 Hz, 1H), 7.54 (s, 1H), 7.63 (s, 1H). MS: (M+H)+=306.2. the mixture was stirred overnight The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min. 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6H), 4.66-4.79 (m, 1H), 6.65 (d, J=3.03 Hz, 1H), 7.27-7.31 (m, 1H), 7.45 (d, J=3.03 Hz, 1H), 7.54 (s, 1H), 7.63 (s, 1H). MS: (M+H)+=306.2. the mixture was stirred overnight The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-6-(trifluoromethyl)-1H-indole (1 g, 3.79 mmol) in DMF (6 mL) was added 60% sodium hydride (0.182 g, 4.54 mmol), and the mixture was stirred for 30 min. 2-bromopropane (0.533 mL, 5.68 mmol) was added and the mixture was stirred overnight. The reaction was then quenched with 10% NaHCO3 and extracted with EtOAc (3×). The extract was dried over Na2SO4 and concentrated. The residue was purified using column chromatography (Silica gel, 0 to 100% EtOAc/hexanes) to give the title compound (460 mg, 40%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.61 (m, 6H), 4.66-4.79 (m, 1H), 6.65 (d, J=3.03 Hz, 1H), 7.27-7.31 (m, 1H), 7.45 (d, J=3.03 Hz, 1H), 7.54 (s, 1H), 7.63 (s, 1H). MS: (M+H)+=306.2. the mixture was stirred overnight The reaction was then quenched with 10% NaHCO3 extracted with EtOAc (3×) The extract was dried over Na2SO4 concentrated The residue was purified