4-Bromo-7-azaindole

Pale yellow powder

1H-pyrrolo[2, 3-b]pridine 7-oxide 21 (3.0 g, 22.4 mmol) and tetramethylammonium (4.13 g, 1.2 eq) were dissolved in DMF (30 ml). The Ms1H-7-N-heteroquinone oxynitride 18b (3.0 g, 22.4 mmol), (Me) 4NBr (4.13 g, 1.2 eq) was dissolved in 30 ml of DMF.Cool to 0 ° C, Ms2O (7.8g, 2.0eq) was added in batches, Stir at 0 ° C for 1 h, Stir at room temperature for 4 h, dilute with 60 ml of water.Dilute the NaOH solution to a pH of 7, add 100ml of ice water, Move to -5 ° C, let stand for 1 h, precipitate a solid, Filter under reduced pressure, wash with ice water, Drying in vacuo gave pale yellow powder 18c (2.47 g, 56percent).A solution of methanesulfonic anhydride (6.066 g, 34.82 mmol) and acetonitrile (1 1.7 mL) was added by drops to a solution of 1 H-pyrrolo[2, 3-b]pyridine 7-oxide (2.333 g, 17.41 mmol), tetramethyl ammonium bromide (4.023 g, 26.12 mmol) in DMF (1 1.7 mL) at O00298] Step B: Tetramethylammonium bromide (72 g, 470 mmol) was added to IH- pyrrolo[2, 3-b]pyridine N-oxide (42 g, 313 mmol) in DMF (500 mL) at 01H-pyrrolo[2, 3-b]pyridine 7-oxide x257 (3.4 g, 25.4 mmol) and tetramethylammonium bromide (4.7 g, 1.2 eq, 30.4 mmol) are dissolved in DMF (33 ml). Then MS2O (8.8 g, 2 eq, 50.8 mmol) is added at 0 [0592] To a stirred solution of tetra methyl ammonium bromide (45 g, 291 mmol) in DMF (182 mL) at 0 °C under an argon atmosphere were added 1H-pyrrolo [2, 3-bj pyridine 7- oxide (26 g, 194 mmol) and methane sulfonic anhydride (67.5 g, 388 mmol). The reaction mixture was warmed to room temperature and stirrematerial (by TLC), the reaction mixture was neutralised with 50percent sodium hydroxide solution to pH above 8-9, diluted with water (400 mL) to obtain the solid. The solid was dissolved in 10percentMeOH/CH2C12 (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with n-pentane (2 x 50 mL) to afford 4-bromo-1H-pyrrolo [2, 3-bj pyridine (15.2 g, 40percent) as an off-white solid. ‘H NMR (DMSO-d6, 500 MHz): 12.01 (br s, 1H), 8.07 (s, 1H), 7.60 (s, 1H), 7.30 (d, 1H), 6.40 (s, 1H), 6.57 (s, 1H); TLC: 5percent MeOH/ CH2C12 (Rj: 0.7).d for 18 h. After consumption of startingc) To a 3 L fixed vessel under an atmosphere of nitrogen was charged methanesulfonic anhydride (363 g, 2042.71 mmol) portionwise to 1H-pyrrolo[2, 3-b]pyridine 7-oxide (137 g, 1021.36 mmol), and tetramethylammonium bromide (236 g, 1532.03 mmol) in DMF (10 vol) (1370 ml) cooled to 0° C. over a period of 30 minutes under nitrogen. The resulting suspension was stirred at 20° C. for 24 hours. The reaction mixture was quenched with water (20 vol, 2740 ml) and the reaction mixture was adjusted to pH 7 with 50percent sodium hydroxide (approx 200 ml). Water (40 vol, 5480 ml) was charged and the mixture cooled to 10° C. for 30 minutes. The solid was filtered, washed with water (20 vol, 2740 ml) and the solid disssolved into DCM/methanol (4:1, 2000 ml), dried over MgSOA solution of trifluoromethyl sulfonic anhydride (9.3 g, 33 mmol) was added dropwise to a mixture of lH-pyrrolo[2, 3- δ]pyridine 7-oxide (3 g, 22 mmol) and tetrabutyl ammonium bromide (10.8 g, 33 mmol) in Λ/, Λ/-dimethylformamide (30 mL) at 0 To a 0 The 1/-/-pyrrolo[2, 3-b]pyridine 7-oxide (3.67 g) and tetramethylammonium bromide (1.5 eq.) were placed in DMF (15 ml). The mixture was cooled to 0°C and methanesulfonic anhydride (2 eq.) was added portion wise. The suspension was allowed to reach RT and stirred for 5.5 hours. The reaction mixture was then poured into water (70 ml) and neutralized with 4M NaOH. Water (60 ml) was added. The product was extracted with DCM, washed with water, dried over MgSO4, filtered. The solvent was evaporated and the residue was purified by flash chromatography on silica gel (DCM to DCM/MeOH 9:1 ) to give the 4-bromo-1 H-pyrrolo[2, 3-b]pyridine as a yellow oil (21 percent yield).Preparation of 1-methyl-4-phenyl-1H-pyrrolo[2, 3-b]pyridine-3-carbaldehyde (Formula 17); A solution of 70percent mCPBA (11.54 g, 66.87 mmole) in ethyl acetate (25 mL) was added by drops to a solution of 7-azaindole (Formula 11, 5 g, 42.3 mmole) in ethyl acetate (40 mL) at 0° C. with a good stirrer. After addition was completed, the mixture was stirred at room temperature for 1 to 2 hours until no starting material left. The mixture was cooled, filtered, and washed with ethyl acetate to give a solid. It was dissolved in 50 mL of water and treated with 30percent K1H- Pyrrolo[2, 3-b]pyridine oxide (50 g, 373 mmol) and tetramethylammonium bromide (86 g, 559 mmol) were stirred into DMF (500 ml_) at room temperature and then cooled to 0

4-Bromo-7-azaindole is an important organic intermediate (building block) to synthetize substituted azaindole products.