3-Bromo-5-chloro-1H-pyrrolo[2,3-b]pyridine

Step 1 : 3-Bromo-5-chloro-lH-pyrrolo[2, 3-b]pyridine. N-Bromosuccinimide (1.08 g, 6.1 mmol) was added to a solution of 5-chloro-lH-pyrrolo[2, 3-]pyridine (0.85 g, 5.5 mmol) in DMF (25 mL) and stirred for 4 h at it. Water (100 mL) was added the mixture extracted with EtOAc (3 x 50 mL), the organics combined, dried over sodium sulfate, filtered and evaporated to dryness. Purification by column chromatography (hex/EtOAc) afforded the desired product (1.28 g, quant.). 1H NMR (400 MHz, DMSO-^) δ ppm 12.3 (br. s), 8.30 (d, 1 H), 7.93 (d, 1H), 7.84 (s, 1H)To a stirred solution of 5-chloro-1H-pyrrolo[2, 3-b]pyridine (1) (50 g, 0.3289 mol) in DMF (200 mL) was added N-bromosuccinimide (70.26 g, 0.3947 mol) by portion wise at 0 °C and stirred for 2 h. After completion of the reaction as indicated by TLC, the reaction mixture was poured into ice cold water (600 mL) to form brown precipitate which was filtered and dried under air to afford 3- bromo-5-chloro-1H-pyrrolo[2, 3-b]pyridine (2) (70 g, 0.3043mol, 92percent yield) as pale brown solid. TLC system: 20percent EtOAc in hexane RA solution of bromine (3.5mol) in chloroform (40mol) was added dropwise to an ice-cold solution of the 5-chloro-1H- pyrrolo[2, 3-b]pyridine (3) (10g, 65mM) in chloroform (260mol). The reaction mixture was stirred for 60 minutes at 0°C. The reaction mixture was then hydrolyse with water and the pH of the solution was adjusted to 10. The resulting solid was removed by filtration, and the. aqueous was extracted with dichloromethane. The organic was washed with water, dried over magnesium sulfate and concentrated in vacuo to afford the title compound (10.5g, 69percent). 1H NMR (DMSO-d6) 7.8 (1H, s), 7.9 (1H, s), 8.3 (1H, s)0.30 g (1.97 mmol) of 5-chloro-lH-pyrrolo[2, 3-b]pyridine was dissolved in 10 mL of methylene chloride to which 0.38 g (2.16 mmol) of N-bromosuccinimide and 0.52 g (2.16 mmol) of dibenzoyl peroxide were added, followed by stirring at room temperature for 18 hours. The precipitated crystals were filtered and then washed with methylene chloride to give 0.24 g (52.0percent yield) of 3-bromo-5-chloro-lH-pyrrolo[2, 3-b] pyridine. 1H NMR (DMSO) δ : 12.32(br s, 1H), 8.28(m, 1H), 7.91 (m, 1H), 7.82(m, 1H)Into a 3000-mL 3-necked round-bottom flask was placed a solution of 5-chloro-1H-pyrrolo[2, 3-b]pyridine (120 g, 784.31 mmol, 1.00 equiv) in AcOH (1200 mL). This was followed by the addition of a solution of B (139 g, 868.75 mmol, 1.10 equiv) in AcOH (600 mL) dropwise with stirring at 90°C over 80 min. The resulting solution was stirred for 1.5 h at 90°C in an oil bath. Then it was cooled and concentrated under vacuum. The residue was adjusted to pH 10 with sodium hydroxide solution (1M). The solid was collected by filtration, then washed with 3x500 ml of water and dried in an oven under reduced pressure. This resulted in 87.2 g (48percent) of 3-bromo-5-cWoro-1H-pyrrolo[2, 3-b]pyridine as a yellow solid.[0231] Step 2: l-(Benzenesulfonyl)-3-bromo-5-chloro-pyrrolo[2, 3-b]pyridine. NaH (60% dispersion in oil, 0.33 g, 8.3 mmol) was added to a solution of 3-bromo-5-chloro-lH- pyrrolo[2, 3-b]pyridine (1.28 g, 5.5 mmol) in DMF (25 mL) at room temperature. The reaction was stirred for 10 min. and then /?-toluenesulfonyl chloride (1.06 mL, 8.3 mmol) was added and the reaction stirred for an additional 2 h. Water (50 mL) was added, the mixture extracted with EtOAc (3 x 50 mL), the organic layers combined, dried over sodium sulfate, filtered and evaporated to dryness. Purification by column chromatography (hex/EtOAc) and recrystallization from hex/EtOAc afforded the desired product (1.45 g, 70%). 1H NMR (400 MHz, DMSO- e) delta ppm 8.50 (d, 1 H), 8.35 (s, 1 H), 8.13 (dd, 1H), 8.12 (d, 2H), 7.76 (dt, 1 H), 7.65 (t, 2 H).

Molecular Weight:231.48
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:229.92464
Monoisotopic Mass:229.92464
Topological Polar Surface Area:28.7
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes