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CAS No. : | 58534-95-5 | MDL No. : | MFCD09864700 |
Formula : | C6H5BrFN | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HYPQOSVTIONWSN-UHFFFAOYSA-N |
M.W : | 190.01 | Pubchem ID : | 22341891 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 100.0℃; for 23h;Inert atmosphere; | Step 2: A flask was charged with 3-bromo-2-fluoroaniline (3.84 g, 20.2 mmol), bis(pinacolato)diboron (6.16 g , 24.25 mmol), potassium acetate (3.96 g, 40.4 mmol), Pd(dppf)Cl2 CH2C12 (495 mg, 0.606 mmol), and DMF (40 mL) under nitrogen atmosphere. After stirring for 23 h at 100 C the reaction mixture was concentrated in vacuo, the residue was triturated with hexanes and filtered through a pad of celite. The filtrate was adsorbed on silica gel. Purification by flash silica gel chromatography using a gradient of 0-30% EtOAc/hexane afforded 3.65 g of pinacol 3-amino-2-fluoroboronate as an off white solid (76% yield): 1H NMR (CDC13, ppm) delta 1.39 (s, 12H), 3.73 (broad s, 2H), 6.91 (dt, 1H), 6.97 (t, 1H), 7.11 (m, 1H). |
60.7% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100.0℃; for 16h;Inert atmosphere; | [0593] To a solution of compound 138 (500 mg, 2.64 mmol), 4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi(1,3,2-dioxaborolane) (806 mg, 3.17 mmol) and KOAc (518 mg, 5.29 mmol) in DMF (10 mL) was added Pd(dppf)Cl2 (108 mg, 0.13 mmol) at room temperature under N2 atmosphere. The reaction was stirred under nitrogen protection at 100 oC for 16 hrs. Water (10 mL) was added and the mixture was extracted with ethyl acetate (20 mL x 2). The combined organic phases are washed with brine, dried over anhydrous Na2SO4, filtered and then concentrated. The residue was purified by column chromatography on silica gel (eluted with Petroleum ether: Ethyl acetate =40: 1) to give the title compound (380 mg, 60.7% yield) as white solid. LC/MS (ESI) m/z: 238 (M+H) + |
803 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90.0℃; for 15h;Inert atmosphere; | [0477] A solution of 3-bromo-2-fluoroaniline (0.5g, 2.63 mmol), 4,4,4,4,5,5,5,5?- octamethyl-2,2?-bi(1,3,2-dioxaborane) (1.67g, 6.6 mmol), and KOAc (0.77g) in dioxane (10 mL) was degassed and refilled with argon twice. To this solution was added Pd(dppf)2C12 (289 mg) under an atmosphere of argon. The solution was heated at 90C for 15 h. The reaction mixture was cooled to rt and the volatiles were removed under reduced pressure. The remaining residue was purified by column chromatography to afford S2 (803 mg). |
6.9 g | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 100.0℃; for 7h;Inert atmosphere; | A mixture of 3-bromo-2-fluoro-phenylamine (6.52 g, 33.63 mmol), bis(pinacolato)diboron (10.45 g, 41.14 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (1 :1) (1.12 g, 1.37 mmol) and potassium acetate (10.1 g, 103.06 mmol) in dry DMF (65 mL) was heated at 100C under an atmosphere of nitrogen for 7 hours. The reaction was allowed to cool to room temperature, diluted with AcOEt and filtered through celite. The organic was washed with water, brine, dried over Na2SO4 and evaporated. The crude was purified by silica gel chromatography which was eluted with hexane:AcOEt = 8:2 to afford 2-fluoro-3-(4,4,5,5- tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-phenylamine (6.90 g) as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With diphenyl phosphoryl azide; triethylamine; In N,N-dimethyl-formamide; at 0℃; for 2h; | Step 1: 3-bromo-2-fluoroaniiTo a stirred solution of 3-bromo-2-fluoro benzoic acid (10 g, 0.04566 mol) in Ν,Ν-dimethyl formamide (80 mL), were added dropwise triethylamine (19 ml_, 0.13669 mol) and diphenylphosphoryl azide (14.8 mL, 0.05378 mol) at 0Csequentially. The reaction mixture was stirred for 2 h at 0C. Water (27 mL) was added and the reaction mixture was heated at 80 C for 2 h. The reaction mixture was cooled to room temperature, diluted with water (200 mL) and extracted with diethyl ether (3x150 mL). The combined organic layers were washed with cold water (2x200 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure.The residue obtained was treated with hexane (100 mL), filtered, and the filter cake was washed with hexane (2x100 mL). The filtrate was evaporated under reduced pressure to afford the title compound (4.3 g, 50%) as a brown liquid. H NMR (400 MHz, DMSO-d6) : δ 6.82-6.70 (m, 3H), 5.43 (brs, 2H); ESI-MS: Calculated mass:188.96; Observed mass: 188.10 [M-H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 80℃; for 17h; | To a degassed solution of 3-bromo-2-fluoroaniline (282a) (2.415 g, 12.71 mmol), 3- chloropyridin-4-ylboronic acid (2.00 g, 12.71 mmol) in ethylene glycol dimethyl ether (50 mL) was added a solution of potassium bicarbonate (4.45 g, 44.5 mmol) in water (2.00 mL) followed by (Pd(dppf)Ch (0.930 g, 1.271 mmol) and mixture was stirred at 80 C for 17 h. The reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organics were dried, filtered, concentrated and purified by chromatography [silica gel 24 g, eluting with EtOAc in hexanes from 0 to 50%] to afford 3-(3-chloropyridin-4-yl)-2-fluoroaniline (329d) (0.189 g, 7 % yield) as a white solid; NMR (300 MHz, DMSO-i) delta 8.75 (d, J= 0.6 Hz, 1H), 8.59 (d, J = 4.9 Hz, 1H), 7.46 (dd, J= 5.0, 0.6 Hz, 1H), 6.99 (td, J = 7.7, 0.7 Hz, 1H), 6.93 - 6.80 (m, 1H), 6.54 - 6.41 (m, 1H), 5.36 (s, 2H, D20 exchangeable);19F NMR (282 MHz, DMSO-d) delta - 137.11; MS (ES+): 223.2 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; In 1,4-dioxane; at 100℃; for 16h; | Combine 3-bromo-2-fluoroaniline (1.9g, 10mmol), <strong>[109-11-5]morpholin-3-one</strong> (847mg, 11mmol), cuprous iodide (476mg, 2.5mmol), trans-N,N'-dimethyl A degassed mixture of 1,2-cyclohexanediamine (710 mg, 5 mmol), potassium phosphate (3.2 g, 15 mmol) in 1,4-dioxane (50 mL) was stirred at 100C for 16 h. The cooled reaction mixture was filtered and concentrated. The residue was partitioned between EtOAc and water. The organic extract was washed with brine, dried (Na2SO4), and concentrated. The residue was purified by silica chromatography (solvent gradient, 80-100% EtOAc in cyclohexane) to give the title compound (1.2 g, 58%) as a light brown solid. |
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