2-BROMO-1-FLUORO-4-IODOBENZENE

light yellow liquid

Into a 1 L four-necked round bottom flask equipped with a stirrer, a Liebig condenser, a 100 mL dropping funnel and a thermometer, 630 mL of water, 84 mL (0.926 mol) of concentrated hydrochloric acid and 54.7 g (0.241 mol) of 3-bromo-4-fluoroaniline were placed and stirred at room temperature for one day.Subsequently, the solution was cooled to -10 ° C. with an ice water bath and an aqueous solution (63 mL) of 19.0 g (0.270 mol) of sodium nitrite was added dropwise at a temperature not exceeding 5 ° C., followed by stirring at 5 ° C. or lower for 30 minutes, And filtered using a filter aid to obtain an aqueous solution of a diazonium salt.Next, 42.0 g (0.251 mol) of potassium iodide and 125 mL of water were placed in a 2 L four-necked round bottom flask equipped with a stirrer, Erlin condenser, 1 L dropping funnel and thermometer, And the mixture was stirred at 10 ° C. Then, after the aqueous solution of the diazonium salt was dropped, the water bath was removed and the temperature was returned to room temperature, then the temperature was raised to 40 ° C., and the mixture was stirred at the same temperature for 4 hours. The resulting reaction solution was returned to room temperature again, 270 mL of DCM was added and the mixture was transferred to a 2 L separatory funnel, then the aqueous layer was separated, and extracted with 220 mL of DCM. Next, the DCM layers were combined, washed with 220 mL of 20percent aqueous sodium thiosulfate solution, 220 mL of saturated aqueous multilayer, 220 mL of water three times, dried with magnesium sulfate, then removed by suction filtration of magnesium sulfate, The solvent was distilled off under reduced pressure. Subsequently, the obtained crude oil was purified by silica gel column chromatography using n-heptane as a developing solvent to obtain 62.5 g (yield 86.0percent) of the target compound.Add at 0 °C a solution of sodium nitrite (2. 0 g, 28. 9 mmol) in water (15 mL) to a suspension of 3-bromo-4-fluorophenylamine (5. 0 g, 26. 3 mmol) in a 6 N aqueous solution of hydrochloric acid (25 mL) at 0 °C slowly over 10 min. Stir the mixture at 0 °C for 5 min. Add this solution to a solution of potassium iodide (4. 37 g, 26. 3 mmol) in water (125 mL) via syringe at 0 °C under nitrogen over 15 min. Stir at 0 °C for 30 min. Warm to room temperature. Extract with four times with dichloromethane (100 mL), dry (sodium sulfate), filter, and concentrate. Purify by silica gel chromatography, eluting with 100 : 0 to 95 : 5 hexanes : ethyl acetate to give the title compound as a colorless oil (5. 83 g, 74percent). 1H NMR (300 MHz, Cd13) 5 6. 82-6. 91 (t, J = 8. 5 Hz, 1H), 7. 54-7. 61 (m, 1H), 7. 83- 7. 90 (dd, J = 2. 1 Hz, J = 6. 4 Hz, 1H).Under argon atmosphere, 4-methylthiophenol (651 mg, 5.25 mmol), Mix A solution of diisopropylethyamine (5 mL) and DMF (7 mL) was sparged with argon for about 15 minutes.1-(difluoromethoxy)-4-ethynyl-2-methylbenzene (1) (550 mg, 3.02 mmol) and Add 9H-purin-2-amine (135 mg, 1 mmol), 7H-pyrrolo[2, 3-d]pyrimidin-2-amine (134 mg, 1.00 mmol), Add QD105 (200g, 0.78mmol), 2-bromo-4-iodo-1-methylbenzene (457mg, 1.54mmol), potassium carbonate(323mg, 2.34mmol) and valine (18mg, 0.16mmol) to the eggplant In the flask, dimethyl sulfoxide was added, andthe reaction solution was deoxidized. Copper iodide (16 mg, 0.08 mmol) was added and the reaction solution was deoxygenated. Heat to 90C and stir for 16 hours. After the reaction was completed, it was cooled to room temperature, water and ethyl acetate were added, and the mixture was filtered over celite. The target compound was obtained in 256 mg.Add QD105 (200 g, 0.78 mmol),

Molecular Weight:300.89
XLogP3:3.4
Hydrogen Bond Acceptor Count:1
Exact Mass:299.84469
Monoisotopic Mass:299.84469
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes