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

a) 16.8g (0.14mol) of 7-azaporphyrin, 24.13g (0.143mol) of 48percent hydrobromic acid, and 260g of methylene chloride were charged into a reaction flask and stirred uniformly to obtain a reaction mixture C;b) The reaction mixture temperature was controlled to 25 ~ 30 ° C, was added dropwise 20percent of 20.20g of hydrogen peroxide to obtain a mixture D;c) mixture D is neutralized with a saturated aqueous solution of 60 g of sodium hydrogen sulfite until the red color in the reaction solution completely disappears, liquid separation, to obtain an organic phase E and an aqueous phase F;d) the organic phase E is washed with water, the amount of water is 200g;e) The organic phase E obtained in the step (d) recovers the dichloromethane solvent to obtain 26.6 g of 5-bromo-7-azaporphyrin product, the yield is 95.6percent, and the product liquid chromatographic purity is ≥99percent;A mixture of 59 g of the compound prepared in step 2 was prepared7-aza-indolineCrude and6.8 g p-toluenesulfonic acid as well600 mL of dichloromethane1L of four bottles, 51.2 g of bromine was added dropwise at room temperature, After dripping at room temperature for 8 h;The reaction solution obtained in Step 3 was washed three times with 0.2 mol / L sodium thiosulfate, The organic phase was dried over anhydrous sodium sulfate, Concentrated 84.8 g of 5-bromo-7-azaindoline product, Yield of about 86percent;A solution OF BR2 (18.1 ML, 56.2 g, 0. 351 mol) in dry CH2CL2 (250 mL) was added dropwise over a period of 1 h 45 min to a stirred and cooled (-5 C) solution of 2 (42. 22 g, 0.351 mol) in dry CH2CL2 (410 ML)-PYRIDINE (40 mL). The yellow suspension WAS STIRRED AT 0 C for 45 min and poured into A mixture of saturated aqueous NaHCO3 (800 ML) and saturated aqueous NA2S203 (100 mL). Methanol (10 ML) was added and the lower organic layer was separated and dried over MGS04. The aqueous layer was extracted with AcOEt: MEOH=99 : 1 (7x1000 mL). These extracts were also dried with MgSO4. The organic solutions were combined and concentrated to afford 5 (59. 17 g, 85percent), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) No. 3. 07 (tt, J = 8.4, 1.1 Hz, 2H), 3.64 (T, J = 8. 4 Hz, 2H), 4.47 (bs, 1H), 7.31 (m, 1H), 7. 85 (dt, J= 2.1, 0.9 Hz, 1H).A mixture of 7-azaindoline (4 g, 33.29 mmol), pyridine (4 mL), and DCM (40 mL) was added BrPreparation Example R-4. Preparation Example O-1. 2, 3-Dihydro-1H-pyrrolo[2, 3-b]pyridine-5-carbonitrile 1H-Pyrrolo[2, 3-b]pyridine (1.0g, 8.46mmol) and 10percent palladium-carbon (500mg) were dissolved in a mixture of formic acid (10mL) and triethylamine (10mL), and the solution was stirred at 70°C for 17 hours. To this reaction mixture was further added 10percent palladium-carbon (270mg), and the mixture was stirred at 70°C for 2 hours. The reaction mixture was cooled to room temperature, then an aqueous solution of 5N sodium hydroxide was added thereto, the solution was extracted with ethyl acetate and tetrahydrofuran, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (ethyl acetate : methanol = 10 : 1), and 2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (614mg, 5.11mmol, 60percent) was obtained as a pale yellow solid. The resulting 2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (614mg, 5.11mmol) and N-bromosuccinimide (1.09g, 6.13mmol) were dissolved in N, N-dimethylformamide (12mL), and the solution was stirred for 2.5 hours at room temperature. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution at 0°C, which was then extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by NH silica gel column chromatography (hexane : ethyl acetate = 3 : 1), and 5-bromo-2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (370mg, 1.86mmol, 36percent) was obtained as a white solid. The resulting 5-bromo-2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (345mg, 1.73mmol), zinc cyanide (305mg, 2.60mmol) and tetrakis(triphenylphosphine)palladium(0) (200mg, 0.173mmol) were dissolved in dimethylsulfoxide (7mL), and the solution was stirred at 120°C for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water and ethyl acetate were added to the reaction solution, the organic layer was separated, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (ethyl acetate), and the title compound (167mg, 1.15mmol, 66percent) was obtained as a light brown solid. Preparation Example O-1. 2, 3-Dihydro-1H-pyrrolo[2, 3-]pyridine-5-carbonitrile 1H-Pyrrolo[2, 3-b]pyridine (1.0g, 8.46mmol) and 10percent palladium-carbon (500mg) were dissolved in a mixture of formic acid (10mL) and triethylamine (10mL), and the solution was stirred at 70°C for 17 hours. To this reaction mixture was further added 10percent palladium-carbon (270mg), and the mixture was stirred at 70°C for 2 hours. The reaction mixture was cooled to room temperature, then an aqueous solution of 5N sodium hydroxide was added thereto, the solution was extracted with ethyl acetate and tetrahydrofuran, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (ethyl acetate : methanol = 10 : 1), and 2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (614mg, 5.11mmol, 60percent) was obtained as a pale yellow solid. The resulting 2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (614mg, 5.11mmol) and N-bromosuccinimide (1.09g, 6.13mmol) were dissolved in N, N-dimethylformamide (12mL), and the solution was stirred for 2.5 hours at room temperature. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution at 0°C, which was then extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by NH silica gel column chromatography (hexane : ethyl acetate = 3 : 1), and 5-bromo-2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (370mg, 1.86mmol, 36percent) was obtained as a white solid. The resulting 5-bromo-2, 3-dihydro-1H-pyrrolo[2, 3-b]pyridine (345mg, 1.73mmol), zinc cyanide (305mg, 2.60mmol) and tetrakis(triphenylphosphine)palladium(0) (200mg, 0.173mmol) were dissolved in dimethylsulfoxide (7mL), and the solution was stirred at 120°C for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water and ethyl acetate were added to the reaction solution, the organic layer was separated, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (ethyl acetate), and the title compound (167mg, 1.15mmol, 66percent) was obtained as a light brown solid. Step 2; A solution of BrControl the temperature below 20 degrees Celsius, dihydro-7-azaindole 120kg dissolved in 1200kg of hydrogen bromide dubbed the solution, Control the temperature of 20-30 degrees Celsius, slowly dropping hydrogen peroxide 120kg, add the continued reaction for 5 hours, and then to the reaction solution by adding sodium hydroxide to adjust, and then filtered, washed, centrifuged 0.5 hours, dried product 130kg dihydro-5-bromine -7-azaindole.

Molecular Weight:199.05
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:197.97926
Monoisotopic Mass:197.97926
Topological Polar Surface Area:24.9
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes