4-Bromoindole-3-carboxaldehyde

In a 500-mL three-neck round-bottom flask, 120 mL of dry N, N-dimethylformamide was added and the temperature was lowered to 0°C. Under vigorous stirring, 11 mL (0.12 mol) of phosphorus oxychloride was slowly added dropwise. Stirring was continued for 5 minutes, and 10 g (0.048πο1) dissolved in 20 g of dry N, N-dimethylformamide was slowly added dropwise. 4-Bromoindole (purity 95percent), After the addition, the cold bath was removed and the reaction continued for 1 h. At this point, the reaction solution became a viscous suspension. 4.7M potassium hydroxide solution was slowly added dropwise to the reaction suspension (incremental speed to maintain the reaction solution at 65-75°C, If the temperature is too high, the bath can be cooled, and the reaction is continued for 6 hours after the addition. Slowly add 20 mL of saturated sodium bicarbonate solution, continue stirring for 5 min, dilute with ethyl acetate and dry. Concentration under reduced pressure to obtain the crude 4-bromoindole-3-carboxaldehyde 12g; Immediately afterwards, acetone (2.5mL/g crude product) was heated and refluxed and dissolved. After the dissolution, petroleum ether (11mL/g crude product) was added. The boiling range of petroleum ether is 60oC-90oC, and immediately white fine needle crystals are precipitated) and frozen at low temperature for 10 min. The temperature of freezing is -5 DEG C. After freezing, it is filtered through a sand funnel and washed with petroleum ether twice. In the absence of crystals, the filtered filtrate was again evaporated by evaporation to dry the solvent and the above crystallization was repeated. After a total of four crystallizations, the white crystals of 4-bromoindole-3-carbaldehyde were combined and allowed to air dry. (10.3 g, yield 95percent);General procedure: To a dried two-neck round-bottom flask containing DMF (0.7mL for 1.10mmol of starting material) chilled in an ice bath, POClGeneral procedure: PCC (1.1 mmol) was added to a stirred solution of 4 (1mmol) in DMF (5 mL) at 100 °C (pre-heated oil bath) and the mixture was stirred at 100 °C for 0.5 h.After cooling, the resulting mixture was added to 10percent aqueous HCl solution, extracted with AcOEt (100mL), washed with brine, and dried over MgSO4. The solvent was removed, and the residue was purifiedby silica gel column chromatography with CH2Cl2 to give 2.General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol, 1.0 equiv), 37percent aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25percent aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g, 2 molpercent), and DMF (2 mL). The flask was fitted with a reflux condenser, and the mixture was stirred at 130 °C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL), and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane–EtOAc).General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N, N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 ° C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally, The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g, The product yield was 94percent.Intermediate 27; 4-Bromo-lH-indole-3-carbaldehyde; POCl

Molecular Weight:224.05
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:222.96328
Monoisotopic Mass:222.96328
Topological Polar Surface Area:32.9
Heavy Atom Count:12
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes