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Chemical Structure| 956700-15-5 Chemical Structure| 956700-15-5

Structure of 956700-15-5

Chemical Structure| 956700-15-5

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Product Details of [ 956700-15-5 ]

CAS No. :956700-15-5
Formula : C9H5BrFNO
M.W : 242.05
SMILES Code : O=C1NC=C(F)C2=C1C=C(Br)C=C2
English Name :7-Bromo-4-fluoroisoquinolin-1(2H)-one
MDL No. :MFCD20526591

Safety of [ 956700-15-5 ]

Application In Synthesis of [ 956700-15-5 ]

* 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.

  • Downstream synthetic route of [ 956700-15-5 ]

[ 956700-15-5 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 223671-15-6 ]
  • [ 956700-15-5 ]
YieldReaction ConditionsOperation in experiment
43% With Selectfluor In acetonitrile at 80℃; for 6h; 193; 237 Preparation of 7-bromo-4-fluoro-2H-isoquinolin-1-one (237a): To a solution of 7-bromo-2H-isoquinolin-l-one (3 g, 13.4 mmol) in ACN (30 mL) was added selectfluor (4.8 g,13.4 mmol) at rt. The reaction mixture was heated to 80 °C and stirred for 6 h. The resulting mixture was cooled to rt and purified by reversed-phase flash chromatography directly to afford the title compound as a yellow solid (1.4 g, 43%). LCMS ESI-MS m/z = 241 [M+H]+.
Multi-step reaction with 2 steps 1: Selectfluor / acetonitrile; water / 96 h / 20 °C 2: methanesulfonic acid / dichloromethane / 16 h / 20 °C
Multi-step reaction with 2 steps 1: Selectfluor / water; acetonitrile / 30 °C 2: methanesulfonic acid / dichloromethane / 20 °C
Multi-step reaction with 2 steps 1: Selectfluor; water / acetonitrile / 30 °C 2: methanesulfonic acid / dichloromethane

  • 2
  • [ 2239309-40-9 ]
  • [ 956700-15-5 ]
YieldReaction ConditionsOperation in experiment
89.5% With methanesulfonic acid In dichloromethane at 20℃; for 16h; 2 Step 2: Synthesis of Compound WXBB-5 Compound WXBB-5-2 (3.00 g, 11.54 mmol, 1.00 eq) and methanesulfonic acid (7.76 g, 80.75 mmol, 5.75 mL, 7.00 eq) were dissolved in dichloromethane (50.00 mL). The mixture was reacted at 20° C. for 16 hours. After the reaction was completed, the reaction solution was added with dichloromethane (15 mL), washed successively with water (20 mL) and saturated brine (20 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was dried on a rotary evaporator under reduced pressure. The obtained crude product was slurried with ethyl acetate (10 mL) at 15° C. for 0.5 hour, filtered and the filter cake was dried. Compound WXBB-5 (2.50 g, 10.33 mmol, 89.50% yield) was obtained as a red solid, 1H NMR (400 MHz, DMSO-d6) ppm 7.46 (d, J=5.77 Hz, 1H) 7.71 (d, J=8.53 Hz, 1H) 8.01 (dd, J=8.53, 1.76 Hz, 1H) 8.30 (s, 1H) 11.37 (br. s., 1H).
86% With methanesulfonic acid In dichloromethane 21.2 Step 2: To a stirred solution of 7-bromo-4-fluoro-3-hydroxyisoquinolin-l(2//)-one (1.50 g, 5.77 mmol) in DCM (15 mL) was added methanesulfonic acid (2.77 g, 28.84 mmol, 1.87 mL). The reaction mixture was stirred at room temperature overnight, diluted with DCM (20 mL) and washed with water (20 mL) and brine (20 mL). The organic phase was dried over anhydrousNa2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with ethyl acetate/petroleum ether from 0 to 80%) to give 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (1.20 g, 86% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 242.1.
  • 3
  • [ 956700-15-5 ]
  • [ 2239309-54-5 ]
YieldReaction ConditionsOperation in experiment
52.23% With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate; acetonitrile at 30℃; 21.3 Step 3: To a stirred solution of 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (500.0 mg, 2.07 mmol) in MeCN/Water (22 mL, 10/1) was added selectfluor (804.4 mg, 2.27 mmol). The reaction mixture was stirred at 30 °C overnight, diluted with 20 mL of water, and extracted with DCM (20 mL x 3). The combined organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with EtOAc:petroleum ether from 0 to 90%) to give 7- bromo-4, 4-difluoro-3 -hydroxy-3, 4-dihydroisoquinolin-l(27/)-one 300.0 mg, 1.08 mmol, 52.23% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 278.1.
52.23% With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate; acetonitrile at 30℃; 21.3 Step 3: To a stirred solution of 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (500.0 mg, 2.07 mmol) in MeCN/Water (22 mL, 10/1) was added selectfluor (804.4 mg, 2.27 mmol). The reaction mixture was stirred at 30 °C overnight, diluted with 20 mL of water, and extracted with DCM (20 mL x 3). The combined organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with EtOAc:petroleum ether from 0 to 90%) to give 7- bromo-4, 4-difluoro-3 -hydroxy-3, 4-dihydroisoquinolin-l(27/)-one 300.0 mg, 1.08 mmol, 52.23% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 278.1.
52.23% With lithium hydroxide monohydrate; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In acetonitrile at 30℃; 21.3 Step 3: To a stirred solution of 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (500.0 mg, 2.07 mmol) in MeCN/Water (22 mL, 10/1) was added selectfluor (804.4 mg, 2.27 mmol). The reaction mixture was stirred at 30 °C overnight, diluted with 20 mL of water, and extracted with DCM (20 mL x 3). The combined organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with EtOAc:petroleum ether from 0 to 90%) to give 7- bromo-4, 4-difluoro-3 -hydroxy-3, 4-dihydroisoquinolin-l(27/)-one 300.0 mg, 1.08 mmol, 52.23% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 278.1.
With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate; acetonitrile at 20℃; for 16h; 003.1 Step 1: Synthesis of Compound WX003-1 Compound WXBB-5 (2.50 g, 10.33 mmol, 1.00 eq) and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (4.39 g, 12.40 mmol, 1.20 eq) were dissolved in acetonitrile (150.00 mL) and water (10.00 mL). The mixture was reacted at 20° C. for 16 hours. After the reaction was completed, the reaction solution was added with water (300 mL), and extracted with dichloromethane (DCM) (300 mL). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was dried on a rotary evaporator under reduced pressure. Compound WX003-1 was obtained, 1H NMR (400 MHz, DMSO-d6) δ ppm 5.06 (d, J=2.51 Hz, 1H) 5.33 (s, 1H) 7.72 (dd, J=8.28, 1.76 Hz, 1H) 7.85 (d, J=8.03 Hz, 1H) 7.99 (d, J=8.53 Hz, 1H) 8.06 (s, 1H) 8.15 (d, J=2.01 Hz, 1H) 9.25 (br. s., 1H).

  • 4
  • [ 956700-15-5 ]
  • [ 2239309-55-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / acetonitrile; lithium hydroxide monohydrate / 16 h / 20 °C 2: methanesulfonic acid; triethylsilane / dichloromethane / 32 h / 15 °C
Multi-step reaction with 2 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / lithium hydroxide monohydrate; acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane
Multi-step reaction with 2 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); lithium hydroxide monohydrate / acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane
  • 5
  • [ 956700-15-5 ]
  • [ 2239309-56-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: Selectfluor / acetonitrile; water / 16 h / 20 °C 2: methanesulfonic acid; triethylsilane / dichloromethane / 32 h / 15 °C 3: 8-quinolinol; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 16 h / 130 °C / Inert atmosphere
  • 6
  • [ 956700-15-5 ]
  • [ 2239308-82-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: Selectfluor / acetonitrile; water / 16 h / 20 °C 2: methanesulfonic acid; triethylsilane / dichloromethane / 32 h / 15 °C 3: 8-quinolinol; copper(l) iodide; potassium carbonate / dimethyl sulfoxide / 16 h / 130 °C / Inert atmosphere 4: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate / 1,4-dioxane / 16 h / 120 °C / Inert atmosphere
YieldReaction ConditionsOperation in experiment
With Selectfluor In N,N-dimethyl acetamide at 150℃; Microwave irradiation; 1 6-Bromo-4-fluoroisoquinolin-1(2H)-one General procedure: A mixture of 6-bromoisoquinolin~1 (2H)-one (385 g, 1.63 mmol), 1-chloromethyl~4~ fluoro-1 ,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) [Selectfluor] (578 mg, 1.63 mmol), and dimethylacetamide (3.5 mL) was heated in a microwave for 15 minutes at 150°C. This was repeated three more times. The four runs were combined and partitioned between EtOAc (100 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2 x 100 mL), and the combined organic extracts were washed with brine, dried (Na2SG4) and concentrated, and the residue was purified by silica chromatography (0-50% EtOAc in Hex) to give the title compound (230 mg, 25%).1H NMR (500 MHz, DMSO-cfe) d ppm 1 1.30 (br s,1 H) 8.12 (dd, 1 H) 7.91 (d, 1 H) 7.78 (dd, 1 H) 7.47 (m, 1 H); MS (m/z): 241.9 [M+1].
  • 8
  • [ 2820196-60-7 ]
  • [ 956700-15-5 ]
YieldReaction ConditionsOperation in experiment
86% With methanesulfonic acid In dichloromethane at 20℃; 21.2 Step 2: To a stirred solution of 7-bromo-4-fluoro-3-hydroxyisoquinolin-l(2//)-one (1.50 g, 5.77 mmol) in DCM (15 mL) was added methanesulfonic acid (2.77 g, 28.84 mmol, 1.87 mL). The reaction mixture was stirred at room temperature overnight, diluted with DCM (20 mL) and washed with water (20 mL) and brine (20 mL). The organic phase was dried over anhydrousNa2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with ethyl acetate/petroleum ether from 0 to 80%) to give 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (1.20 g, 86% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 242.1.
86% With methanesulfonic acid In dichloromethane at 20℃; 21.2 Step 2: To a stirred solution of 7-bromo-4-fluoro-3-hydroxyisoquinolin-l(2//)-one (1.50 g, 5.77 mmol) in DCM (15 mL) was added methanesulfonic acid (2.77 g, 28.84 mmol, 1.87 mL). The reaction mixture was stirred at room temperature overnight, diluted with DCM (20 mL) and washed with water (20 mL) and brine (20 mL). The organic phase was dried over anhydrousNa2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with ethyl acetate/petroleum ether from 0 to 80%) to give 7-bromo-4- I uoroi soqui nol i n- 1 (2/7)-onc (1.20 g, 86% yield) as a light yellow solid. LC-MS (ESI) [(M+H)+]: 242.1.
  • 9
  • [ 956700-15-5 ]
  • [ 2820195-77-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / lithium hydroxide monohydrate; acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); lithium hydroxide monohydrate / acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere
  • 10
  • [ 956700-15-5 ]
  • [ 2820196-61-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / lithium hydroxide monohydrate; acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); lithium hydroxide monohydrate / acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere
  • 11
  • [ 956700-15-5 ]
  • [ 2820195-78-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / lithium hydroxide monohydrate; acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere 4: ammonium carbamate; [bis(acetoxy)iodo]benzene / methanol / 5 h / 25 °C
Multi-step reaction with 4 steps 1: 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); lithium hydroxide monohydrate / acetonitrile / 30 °C 2: methanesulfonic acid; triethylsilane / dichloromethane 3: potassium carbonate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,4-dioxane; lithium hydroxide monohydrate / 4 h / 100 °C / Inert atmosphere 4: ammonium carbamate; [bis(acetoxy)iodo]benzene / methanol / 5 h / 25 °C
 

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