5-bromo-2-methyl-1H-indole

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 5-bromo-2-methyl-1H-indole (1.5 g, 7.14 mmol) in 10 mL of DMF was added 60% sodium hydride in mineral oil (189 mg, 7.9 mmol). Once hydrogen gas evolution ceased, the mixture stirred for 10 minutes and was then treated with 1 mL (7.83 mmol) of benzene sulfonyl chloride. The reaction was monitored by TLC (ethyl acetate-hexanes (5:95)) to afford a major new slightly less polar product than starting material. After 2 hours, the mixture was poured into 50 mL of saturated aqueous ammonium chloride solution and extracted with three 50 mL portions of ethyl acetate. The combined organic layers were washed with four 25 mL portions of brine, dried over magnesium sulfate, treated with activated carbon (NORIT A™), filtered through diatomaceous earth, and concentrated in vacuo. The residue was adsorbed onto silica gel and chromatographed on silica gel using ethyl acetate-hexanes (1:99, then 2:98, then 3:97) to afford 1.71 g (68.4% yield) of 1-benzenesulfonyl-5-bromo-2-methyl-1H-indole as a clear oil. to afford a major new slightly less polar product After 2 hours extracted with three 50 mL portions of ethyl acetate The combined organic layers were washed with four 25 mL portions of brine dried over magnesium sulfate treated with activated carbon (NORIT A™), filtered through diatomaceous earth concentrated in vacuo chromatographed on silica gel

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

Procedure: 3-(2-Methyl-1H-indol-5-yl)-3-phenyl-acrylic acid ethyl ester LXVII (1.25 g, 57%) was prepared from 2-methyl-5-bromoindole using the procedure described above for 3-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (see Example 14).

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

Procedure: 3-(2-Methyl-1H-indol-5-yl)-3-phenyl-acrylic acid ethyl ester LXVII (1.25 g, 57%) was prepared from 2-methyl-5-bromoindole using the procedure described above for 3-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (see Example 14).

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

Procedure: 5-Bromo-2-methylindole (4.2 g, 200.0 mmol), di-t-butylcarbonate (4.37 g, 20 mmol), 4-dimethylaminopyridine (2.93 g, 24 mmol) and CH3CN (50 mL) were mixed and stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc (300 mL) and the organic solution was washed successively with water (50 mL), a 1N HCl solution (50 mL), a saturated NaHCO3 solution (2×50 mL) and brine (25 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford an oil (6.11 g, 99% yield): 1H NMR (CDCl3, 300 MHz): 7.98 (d, 1H, J=9), 7.56 (d, 1H, J=1), 7.32 (dd, H, J=9, 1), 6.27 (s, 1H), 2.60 (d, 3H, J=1), 1.69 (s, 9H). the organic solution was washed successively with water (50 mL) The organic layer was dried over MgSO4 filtered concentrated in vacuo

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

Procedure: 5-Bromo-2-methylindole (4.2 g, 200.0 mmol), di-t-butylcarbonate (4.37 g, 20 mmol), 4-dimethylaminopyridine (2.93 g, 24 mmol) and CH3CN (50 mL) were mixed and stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc (300 mL) and the organic solution was washed successively with water (50 mL), a 1N HCl solution (50 mL), a saturated NaHCO3 solution (2×50 mL) and brine (25 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford an oil (6.11 g, 99% yield): 1H NMR (CDCl3, 300 MHz): 7.98 (d, 1H, J=9), 7.56 (d, 1H, J=1), 7.32 (dd, H, J=9, 1), 6.27 (s, 1H), 2.60 (d, 3H, J=1), 1.69 (s, 9H). the organic solution was washed successively with water (50 mL) The organic layer was dried over MgSO4 filtered concentrated in vacuo

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

Procedure: To a solution of 5-bromo-2-methyl-1H-indole (1.5 g, 7.14 mmol) in 10 mL of DMF was added 60% sodium hydride in mineral oil (189 mg, 7.9 mmol). Once hydrogen gas evolution ceased, the mixture stirred for 10 minutes and was then treated with 1 mL (7.83 mmol) of benzene sulfonyl chloride. The reaction was monitored by TLC (ethyl acetate-hexanes (5:95)) to afford a major new slightly less polar product than starting material. After 2 hours, the mixture was poured into 50 mL of saturated aqueous ammonium chloride solution and extracted with three 50 mL portions of ethyl acetate. The combined organic layers were washed with four 25 mL portions of brine, dried over magnesium sulfate, treated with activated carbon (NORIT A™), filtered through diatomaceous earth, and concentrated in vacuo. The residue was adsorbed onto silica gel and chromatographed on silica gel using ethyl acetate-hexanes (1:99, then 2:98, then 3:97) to afford 1.71 g (68.4% yield) of 1-benzenesulfonyl-5-bromo-2-methyl-1H-indole as a clear oil. to afford a major new slightly less polar product After 2 hours extracted with three 50 mL portions of ethyl acetate The combined organic layers were washed with four 25 mL portions of brine dried over magnesium sulfate treated with activated carbon (NORIT A™), filtered through diatomaceous earth concentrated in vacuo chromatographed on silica gel

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

Procedure: To a solution of 5-bromo-2-methyl-1H-indole (1.5 g, 7.14 mmol) in 10 mL of DMF was added 60% sodium hydride in mineral oil (189 mg, 7.9 mmol). Once hydrogen gas evolution ceased, the mixture stirred for 10 minutes and was then treated with 1 mL (7.83 mmol) of benzene sulfonyl chloride. The reaction was monitored by TLC (ethyl acetate-hexanes (5:95)) to afford a major new slightly less polar product than starting material. After 2 hours, the mixture was poured into 50 mL of saturated aqueous ammonium chloride solution and extracted with three 50 mL portions of ethyl acetate. The combined organic layers were washed with four 25 mL portions of brine, dried over magnesium sulfate, treated with activated carbon (NORIT A™), filtered through diatomaceous earth, and concentrated in vacuo. The residue was adsorbed onto silica gel and chromatographed on silica gel using ethyl acetate-hexanes (1:99, then 2:98, then 3:97) to afford 1.71 g (68.4% yield) of 1-benzenesulfonyl-5-bromo-2-methyl-1H-indole as a clear oil. to afford a major new slightly less polar product After 2 hours extracted with three 50 mL portions of ethyl acetate The combined organic layers were washed with four 25 mL portions of brine dried over magnesium sulfate treated with activated carbon (NORIT A™), filtered through diatomaceous earth concentrated in vacuo chromatographed on silica gel

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

Procedure: 3-(2-Methyl-1H-indol-5-yl)-3-phenyl-acrylic acid ethyl ester LXVII (1.25 g, 57%) was prepared from 2-methyl-5-bromoindole using the procedure described above for 3-(3-cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (see Example 14).

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

Procedure: A solution of 5-bromo-2-methyl-1H-indole (5.04 g, 24 mmol) in THF (25 mL) was added dropwise to a suspension of potassium hydride (3.2 g, 24 mmol) in THF at 0° C. After fifteen minutes at 0° C., the solution was cooled to −78° C. and a t-butyl lithium solution (1.7 M in pentane, 28.2 mL, 48 mmol) was added dropwise via syringe while maintaining the temperature below −55° C. After an additional 15 minutes, the solution was cooled to −78° C. and treated with a 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (9.8 mL, 48 mmol) dropwise via syringe. The solution was stirred at −78° C. for 1.5 hours, allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride. The solution was diluted with ethyl acetate and filtered to remove inorganic material. The filtrate was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO4) and concentrated. The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes to give 3.9 g (63% yield) of the desired product. MS (ESI(+)) m/e 258 (M+H)+. After fifteen minutes at 0° C. while maintaining the temperature below −55° C the solution was cooled to −78° C. to warm to room temperature quenched with saturated aqueous ammonium chloride The solution was diluted with ethyl acetate filtered to remove inorganic material The filtrate was extracted with ethyl acetate The combined organics were washed with brine dried (MgSO4) concentrated The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes

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

Procedure: A solution of 5-bromo-2-methyl-1H-indole (5.04 g, 24 mmol) in THF (25 mL) was added dropwise to a suspension of potassium hydride (3.2 g, 24 mmol) in THF at 0° C. After fifteen minutes at 0° C., the solution was cooled to −78° C. and a t-butyl lithium solution (1.7 M in pentane, 28.2 mL, 48 mmol) was added dropwise via syringe while maintaining the temperature below −55° C. After an additional 15 minutes, the solution was cooled to −78° C. and treated with a 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (9.8 mL, 48 mmol) dropwise via syringe. The solution was stirred at −78° C. for 1.5 hours, allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride. The solution was diluted with ethyl acetate and filtered to remove inorganic material. The filtrate was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO4) and concentrated. The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes to give 3.9 g (63% yield) of the desired product. MS (ESI(+)) m/e 258 (M+H)+. After fifteen minutes at 0° C. while maintaining the temperature below −55° C the solution was cooled to −78° C. to warm to room temperature quenched with saturated aqueous ammonium chloride The solution was diluted with ethyl acetate filtered to remove inorganic material The filtrate was extracted with ethyl acetate The combined organics were washed with brine dried (MgSO4) concentrated The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes

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

Procedure: A solution of 5-bromo-2-methyl-1H-indole (5.04 g, 24 mmol) in THF (25 mL) was added dropwise to a suspension of potassium hydride (3.2 g, 24 mmol) in THF at 0° C. After fifteen minutes at 0° C., the solution was cooled to −78° C. and a t-butyl lithium solution (1.7 M in pentane, 28.2 mL, 48 mmol) was added dropwise via syringe while maintaining the temperature below −55° C. After an additional 15 minutes, the solution was cooled to −78° C. and treated with a 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (9.8 mL, 48 mmol) dropwise via syringe. The solution was stirred at −78° C. for 1.5 hours, allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride. The solution was diluted with ethyl acetate and filtered to remove inorganic material. The filtrate was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO4) and concentrated. The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes to give 3.9 g (63% yield) of the desired product. MS (ESI(+)) m/e 258 (M+H)+. After fifteen minutes at 0° C. while maintaining the temperature below −55° C the solution was cooled to −78° C. to warm to room temperature quenched with saturated aqueous ammonium chloride The solution was diluted with ethyl acetate filtered to remove inorganic material The filtrate was extracted with ethyl acetate The combined organics were washed with brine dried (MgSO4) concentrated The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes