5-Bromo-1-methyl-1H-indole

2. To solution of 5-bromo-lH-indole (2.08 g, 10.6 mmol) in 35 mL of DMF, was added sodium hydride (60 wtpercent dispersion, 467 mg, 11.67 mmol) at 0 °C. After 30 min, iodomethane(663 μL·, 10.6 mmol) was added. The reaction mixture was allowed warm to RT, and stirred atRT for 10 min. The reaction was quenched with water at 0 °C, and extracted with EtOAc (x3).The combined organic extracts were dried (MgS0General procedure: Indoles were methylated by a similar procedure to that reported in the literature.26 To a stirred suspension of NaH (60percent dispersion inmineral oil; 480 mg, 12.0 mmol) in DMF (10 mL) was added dropwise a solution of an indole (10.0 mmol) in DMF (10 mL) at 0 °C, and the mixture was stirred at room temperature for 30 min. To the mixture was added dropwise iodomethane (d 2.28; 934 mL, 15.0 mmol) at 0 °C, and the resulting mixture was stirred at room temperature overnight. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over MgSO4 and evaporated to leave a residue, which was purified by column chromatography using the indicated eluent.Potassium hydroxide (5.74 g, 102 mmol) was dissolved in dimethylsulfoxide (85 mL) and cooled in an ice bath. 5-Bromoindole (5.00 g, 26 mmol) was added portionwise and the reaction mixture stirred for 1 h before the dropwise addition of iodomethane (7.22 g, 51 mmol). After 45 min the solution was diluted with water (85 mL). The aqueous layer was extracted with diethyl ether (3 x 50 mL). The organic layer was then washed with water (2 x 50 mL), brine (2 x 50 mL) and dried (MgSOTo a stirred slurry solution of NaH (1.54 g, 1.2 eq) in THE (10 mL) at 0CC, 5-bromo- 1H-indole (5.0 g, 1.0 eq) in THE (10 mL) was added drop wise and stirred for about15 mm. Then, 0H31 (2.4 ml, 1.2 eq) was added drop wise and the resulting mixture was stirred at same temperature for about 15 mm, slowly raising the temperature of the mixture to room temperature. The mixture is continued to be stirred for another 30 mm. The reaction mixture was quenched with ice water and extracted with ethyl acetate, the combined organic layer and washed with 1 N HCI solution and water, dried and concentrated to yield the title product (5.1 g, 95.29percent) as a brownish oily mass.To a solution of compound 5-1 (5 g, 25.5 mmol) in dry DMF (100 mL) was added sodium hydride (NaH) (1.53 g, 38.26 mmol) under nitrogen atmosphere in an ice bath (0° C.), and then the reaction solution was warmed to r.t. and was reacted for 0.5 h. To this solution, all MeI (7.24 g, 38.26 mmol) was added at once and then the resulting solution was reacted at r.t. for 1 h. The reaction was monitored by TLC until the completion of reaction. Then saturated NHIn a dry flask under argon, 5-bromoindole (ab) (1.5 g, 7.65 mmol) was dissolved in dry DMF (15 mL). After cooling this mixture to 0 °C, sodium hydride (367 mg, 9.18 mmol, 60percent in oil) was added to form the anion. This solution was stirred at 0 °C for 30 minutes. Then, methyl iodide (0.525 mL, 1.196 g, 8.42 mmol) was added. The resulting mixture was then stirred at room temperature for 5 hours and quenched with water. After dilution in ethyl acetate and separation, the organic layer was washed with brine three times, dried over anhydrous MgSO4 and concentrated. The desired product (ia) (1.24 g, 5.9 mmol) was obtained as a yellow solid. Yield: 77percent. DMF (15 mL). After cooling this mixture to 0 °C, sodium hydride (367 mg, 9.18 mmol, 60percent in oil) was added to form the anion. This solution was stirred at 0 °C for 30 minutes. Then, methyl iodide (0.525 mL, 1.196 g, 8.42 mmol) was added. The resulting mixture was then stirred at room temperature for 5 hours and quenched with water. After dilution in ethyl acetate and separation, the organic layer was washed with brine three times, dried over anhydrous MgS0To a solution of 5-bromoindole (1.0 g, 5.10 mmol) in DMC (10 ML), DABCO (0.057 g, 0.51 mmol) is added followed by DMF (1 ML).The resulting solution is heated to 90-95° C. for 5 h.The reaction is cooled to RT, and diluted with ethyl acetate (EtOAc, 50 ML) and H2O (50 ML).The organic layer is separated and washed in sequence with H2O (50 ML), 10percent aqueous citric acid (2*50 ML) and H2O (4*50 ML).The organic layer is dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under vacuum to give 5-bromo-1-methylindole (about 1.06 g, 99percent) as a golden colored solid: 1H NMR (CDCl3) δ 7.72 (d, 1H), 7.26 (dd, 1H), 7.13 (d, 1H), 7.00 (d, 1H), 6.39 (d, 1H), 3.71 (s, 3H); 13C NMR (CDCl3) δ 135.3, 130.1, 129.9, 124.2, 123.2, 112.6, 110.6, 100.5, 32.9; MS m/z 209 [M+1]+. General procedure: Sodium hydride (60percent in mineral oil, 1.10 equiv) was suspended in DMF [0.6 M]. 1H-Indole (1.00 equiv)was solubilized in DMF [1.0 M] and added to the suspension at 0 °C. The mixture was stirred at rt for 30min. Bromoalkyl or TMSCl (1.50 equiv) was diluted in DMF [3.0 M] and added to the solution at 0 °C.The mixture was stirred at rt for 1 hour. The solution was quenched with water (20 mL) and extractedthree times with EtOAc (10 mL). The organic layers were combined, dried over MgSO4 and concentratedunder reduced pressure. The liquid was filtered through a 5 cm pad of silica with 100percent pentane or Et2O toafforded the title compound.General procedure: NaH (6.1 mmol, 1.2 equiv) was slowly added to a solution of 5-bromoindole/indazole (5.1 mmol, 1 equiv) in DMF (10 mL) at 0 °C. The mixture was stirred at 0 °C for 10 min then the alkylhalide (6.1 mmol, 1.2 equiv) was added at the same temperature. The reaction mixture wascontinued to stir at rt for 2 h. When the reaction was complete [TLC (EtOAc/hexane 1:5)], themixture was extracted with EtOAc (2 × 20 mL) and washed with water (2 × 20 mL). The organiclayer was separated, dried over anhydrous Na2SO4 and the solvent removed under reducedpressure. The residue obtained was purified by flash column chromatography [silica gel (230–400 mesh; Merck), EtOAc/hexane 1:5].General procedure: To a stirring solution of N-methylated substrate (0.1-0.6 mmol, 1.0 eq.) in dioxane (0.034 M) at 73

Molecular Weight:210.07
XLogP3:3.4
Exact Mass:208.98401
Monoisotopic Mass:208.98401
Topological Polar Surface Area:4.9
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes