5-BROMO-3-METHYLINDOLE

(d) 5, 5-Dibromo-3, 3-dimethyl-2, 2-diindolylmethane (42). To a solution of aldehyde 40 (1.51 g, 6.74 mmol) in THF (35 mL) was added LiAlH4 (0.51 g, 13.48 mmol) at 0° C. and then heated to 65-70° C. for 2 h under argon. The suspension was cooled to 0° C. and quenched with water, and white precipitate was removed by filtration. The filtrate was dried (MgSO4) and concentrated to afford 5-bromo-3-methylindole (41) as a solid (1.16 g, 82percent). To a mixture of 39 (1.2 g, 5.0 mmol) and 41 (1.0 g, 4.76 mmol) in CH2Cl2 (25 mL) was added (CF3SO3)3Sc (0.23 g, 0.47 mmol) and stirred overnight under argon. The solvent was evaporated to give a crude product. Flash chromatography (10percent EtOAc/hexane) yielded 42 as a white solid (1.91 g, 93percent): 1H NMR (300 MHz, CDCl3) δ 2.29 (s, 6, CH3), 4.21 (s, 2, CH2), 7.08 (d, J=8.5 Hz, 2, ArH), 7.22 (dd, J=1.8, 8.5 Hz, 2, ArH), 7.66 (d, J=1.8 Hz, 2, ArH), 7.67 (br.s, 2, NH).Ste 2. 5-Bromo-3-methyl-7H-indoleTo a solution of 5-bromo-7H-indole-3-carbaldehyde (5.0 g, 22.3 mmol) in THF (80 mL) was added L1AIHA solution of 5-bromo-1H-indole-3-carbaldehyde (13.12 g, 58.6 mmol) in THF (100 mL) was added to a refluxing mixture of LiA1H4 (4.89 g, 129 mmol) in THF (100 mL) (reflux condenser fitted to a two neck flask) over 30 mm. The reaction mixture was refluxed for 8 hours, cooled to room temperature and treated with diethyl ether (50 mL). The reaction mixture was acidified to pH 3 with iN HC1, while cooling in an ice bath. The reaction mixture was diluted with ethyl acetate (125 mL), poured into a separatory funnel and washed with water (2X 50 mL) and saturated aqueous sodium chloridesolution (50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give crude product. The crude product was dissolved in a small amount of DCM and charged to an ISCO silica gel (80 g) column, which was eluted over 15 minutes using a gradient of 0-50percent ethyl acetate/heptane. The combined fractions were concentrated to give 5-bromo-3-methyl-1H-indole (5.5 g, 44.7percent yield). LCretention time 1.0 mm [Method Al]. MS (E) m/z: 210/212 (M-H).General procedure: 5-Fluoro-1H-indole-3-carbaldehyde (3.2 g, 19.6 mmol) was dissolved in 10 mL of anhydrous tetrahydrofuran, then lithium aluminium hydride (2.61 g, 68.6 mmol) was added to the solution. The mixture was reacted at 70 C for 2 hours. After the reaction, the reaction mixture was cooled to RT and quenched with aqueous sodium hydroxide (18 mL, 2 0%). 60 mL of dichloromethane was added to the mixture and the resulting mixture was washed with saturated aqueous sodium chloride (40 mL). The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EA(V/V)=50/1 to give the title compound as a light yellow solid (2.41 g, 82.3%). The compound was characterized by the following spectroscopic data:General procedure: This method is a general method. To a dry flask, LiAlH4 (15.0 mmol) was added, and TauHF (30.0 mL) was used as a solvent. The above-mentioned crude indole-3-formaldehyde THF (30.0 mL) solution was added dropwise under ice-water bath, and the mixture was allowed to react to room temperature for about 8 hours. The reaction was completely monitored by TLC. To the flask was added 1.0 mL of ice water, and then 1.5 g of NaOH solid and 3.0 mL of water were slowly added. After the reaction was completed, the mixture was stirred at room temperature for about 15 minutes, then the solid was filtered, and the filtrate was extracted with ethyl acetate. (3X 20.0 mL). After EtOAc (EtOAc/EtOAc/EtOAc. The desired 3-methylindoles and derivatives are obtained.General procedure: To a solution of the corresponding pyrrole or indole derivative (10 mmol) in MeCN (30 ml) was added sodium hydroxide (2.00 g, 50 mmol) and tetrabutylamonium hydrogen sulfate (0.17 g, 0.5 mmol). After the solution was stirred at room temperature for 30 min, 2-chloroethylamine hydrochloride (1.39 g, 12 mmol) was added. Then the reaction mixture was refluxed for 24 h. The mixture was poured into water (100 ml), extracted with diethyl ether, dried under MgSO4, and concentrated under reduced pressure to give a crude product. The crude was then purified by flash column chromatography on silica gel (eluted with petroleum ether / ethyl acetate=1 : 1) to give the pure product.

Molecular Weight:210.07
XLogP3:3.3
Hydrogen Bond Donor Count:1
Exact Mass:208.98401
Monoisotopic Mass:208.98401
Topological Polar Surface Area:15.8
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes