5-BROMO-1-TRIISOPROPYLSILANYL-1H-PYRROLO[2,3-B]PYRIDINE

5-Bromo-I-(triisopropylsilyl)-lH-pyrrolo[2, 3-b]pyridine:; Sodium hydride (0.63 g, 25.15 mol) was added in small portion to a stirred solution of 5-bromo-7-azaindole (3.3 g, 16.75 mmmol) in THF (50 mL) at room temperature and the resulting suspension was stirred at room temperature for 15 min. Triisopropylsilyl chloride (5.3 mL, 25.15 mmol) was added and the mixture was heated at 80 °C for 3h. The solvent was evaporated and the residue was dissolved in water (50 mL). The aqueous layer was extracted with EtOAc (3X50 mL), dried (Na2S04) and concentrated under reduced pressure. The crude product was purified by Biotage HPFC system (10percent EtOAc/Hexane) to afford the desired 5-bromo-1- (triisopropylsilyl)-lH-pyrrolo[2, 3-b]pyridine as a white solid (5.2g, 88percent). ; Mass Spec 355 (M+1).The commercially available 5-bromo-1H-pyrrolo[2, 3-b]pyridine x253 (0.94 g, 4.77 mmol) is dissolved in freshly distilled absolute 1 , 2-dimethoxyethane (15 ml). Then 100 percent NaH (0.126 g, 1.1 eq, 5.25 mmol, obtained by washing a 60percent NaH emulsion with hexane in a flow of argon) is added at 0 Step 4; To a stirred solution of 5-bromo- 1 H-pyrrolo[2, 3-b]pyridine (1.5 g, 7.5 mmole) in 15 ml of dioxane and 5 ml of DMF, sodium hydride ( 345 mg, 9 mmole) was added portionwise and, after 0.5 hrs., TIPSCI (2.5 ml, 12.3 mmole); the reaction was stirred at r.t. overnight, then diluted with water and extracted with methylene chloride; a fast purification by silica gel chromatography with dichloromethane gave 2.6 g of 5-bromo-1-triisopropylsilanyl- 1H-pyrrolo[2, 3-b]pyridine (4) (97percent yield). This product was used for the following reaction without any further purification.A Schlenk tube was charged with sodium hydride (95percent pure, 282 mg, 11.15 mmol) anddry THF (12 mL) under argon. The suspension was cooled to 0 °C in an ice bath and 5-bromo-1H-pyrrolo[2, 3-b]pyridin2 (96 percent pure, 2.00 g, 9.74 mmol) was slowly added as aS 11solution in dry THF (20 mL). After 15 min, chloro-triisopropylsilane (95percent pure, 1.96 g, 10.15 mmol) was added as a solution in dry THF (6 mL) at 0 °C and the ice bath wasremoved. At room temperature saturated aqueous solution of ammonium chloride (30 mL)was added and the resulting mixture was extracted with cyclohexane (2 × 100 mL). Thecombined organic phases were dried over MgSO4, and evaporated. Column chromatographicpurification (SiO2, CH/EtOAc, 19:1) yielded a colorless, crystalline solid [3.25 g, 94percent yield].MP: 59 – 60 °C (CH/EtOAc).1H-NMR (400 MHz, CDCl3): δ = 1.11 (d, 3JH, H = 7.6 Hz, 18H, 13-CH3), 1.83 (sep, 3JH, H = 7.6Hz, 3H, 12-CH), 6.49 (d, 3JH, H = 3.5 Hz, 1H, 3-CH), 7.30 (d, 3JH, H = 3.5 Hz, 1H, 2-CH), 7.98(d, 4JH, H = 2.2 Hz, 1H, 4-CH), 8.27 (d, 4JH, H = 2.2 Hz, 1H, 6-CH) ppm.13C-NMR (101 MHz, CDCl3): δ = 12.3 (d, C-12), 18.2 (q, C-13), 102.6 (d, C-3), 112.2 (s, C-5), 124.2 (s, C-9), 129.9 (d, C-2), 132.8 (d, C-4), 142.9 (d, C-6), 152.3 (s, C-8) ppm.ESI(+)-MS: calcd. for C16H25BrN2Si + H+, 353.1044/355.1023; found 353.1039/355.1017.At room temperature, 400 ml of N, N-dimethylformamide was added to a 1 L three-necked flask to start stirring. Add 5_bromo-7-azaindole (30g, 0.15mol) and potassium tert-butoxide (25·6g, 0 · 23mol) to the reaction flask. After stirring and clearing, cool the ice bath to wait for the internal temperature. At 0 °C, triisopropylsilyl chloride (43.3 g, 0.225 mol) diluted with 80 ml of tetrahydrofuran was initially added dropwise. After the addition is completed, the reaction is maintained at 0-5 °C for 10-20 minutes. TLC control, the reaction is over. 300 ml of water was added to the reaction flask, and the mixture was stirred for 15 minutes. The aqueous phase was extracted with methyl tert-butyl ether (200 ml*2). The organic phase was combined and the organic phase was washed with 500 ml of saturated aqueous sodium chloride solution once. After drying over anhydrous sodium sulfate, the solvent is concentrated to obtain an oil, and 50 ml of methanol is added to precipitate a solid. The solid is vacuum filtered and dried to obtain a compound of the formula. Yield: 50.5 g, yield: 93.8percent.Step 1-Preparation of 5-bromo-1-triisopropylsitaoyl-1H-pyrrolo[2, 3-b]pyridine (2)To 5-bromo-7-azaindole (1, 1.5 g, 7.6 mmol) in N, N-dimethylformamide (20 mL) were added sodium hydride (60percent in mineral oil, 0.27 g, 11.0 mmol) and trriisopropylsilyl chloride (2.6 mL, 12.0 mmol), under an atmosphere of nitrogen. The reaction was stirred for 2 hours at room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10percent ethyl acetate in hexane to give the compound (2, 1.6 g, 59percent). MS (ESI)[M+HTo 5-bromo-7-azaindole (67, 1.5 g, 7.6 mmol) in N, N-dimethylformamide (20 mL) were added sodium hydride (60percent in mineral oil, 0.27 g, 11.0 mmol) and trriisopropylsilyl chloride ( 2.6 mL, 12.0 mmol), under an atmosphere of nitrogen. The reaction was stirred for 2 hours at room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 10 percent ethyl acetate in hexane to give the compound (68, 1.6 g, 59percent). MS(ESI)[M+H

Molecular Weight:353.37
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:4
Exact Mass:352.09704
Monoisotopic Mass:352.09704
Topological Polar Surface Area:17.8
Heavy Atom Count:20
Complexity:311
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes