Ethanol → 3-Fluoro-4-(isoquinolin-5-yl)benzenamine

HRID 2356366Notes

Reaction equation

HRID 2356366 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[F:9].[CH:10]1[C:19]2[CH:18]=[CH:17][CH:16]=[C:15](B(O)O)[C:14]=2[CH:13]=[CH:12][N:11]=1.CCO.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:9][C:3]1[CH:4]=[C:5]([NH2:8])[CH:6]=[CH:7][C:2]=1[C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[CH:13]=[CH:12][N:11]=[CH:10]2

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 599474Isoquinoline-5-boronic acidHCID 8218484-Bromo-3-fluoroaniline

Product 1

HCID 593839363-Fluoro-4-(isoquinolin-5-yl)benzenamineYield 82.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

4-Bromo-3-fluorobenzenamine (2.51 g, 13 mmol) and 5-isoquinolineboronic acid (4.23 g, 24 mmol) were suspended in toluene (35 ml) and EtOH (35 ml) and tetrakis(triphenylphosphine)palladium (812 mg, 0.70 mmol) was added, followed by 10% aqueous sodium carbonate (40 ml). The flask was fitted with a reflux condenser and placed in a preheated oil bath (110 C) and stirred under nitrogen for 4 hours. The reaction was then cooled to room temperature, partially concentrated, and diluted with water. The aqueous phase was extracted with DCM, and the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on silica gel (50:1->30:1->20:1 DCM/MeOH). The fractions with product were collected, concentrated, and washed with DCM and hexanes. The remaining solid was dried under high vacuum to afford the desired 3-fluoro-4-(isoquinolin-5-yl)benzenamine (2.568 g, 10.78 mmol, 94% purity, 82% yield). MS (ESI pos. ion) m/z: 497 (MH+). Calc'd exact mass for C15H11FN2: 239. 1H NMR (400 MHz, CDCl3): 9.30 (s, 1H), 8.50 (dd, J=6.0 Hz, 2.0 Hz, 1H), 8.02-7.96 (m, 1H), 7.68-7.63 (m, 2H), 7.58-7.54 (m, 1H), 7.16 (dt, J=8.0 Hz, 2.0 Hz, 1H), 6.61 (dt, J=8.0 Hz, 2.0 Hz, 1H), 6.56 (dt, J=11.5 Hz, 2.0 Hz, 1H), 3.93 (br s, 2H).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. concentrationpartially concentrated
  4. additiondiluted with water
  5. extractionThe aqueous phase was extracted with DCM
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on silica gel (50:1->30:1->20:1 DCM/MeOH)
  10. customThe fractions with product were collected
  11. concentrationconcentrated
  12. washwashed with DCM and hexanes
  13. customThe remaining solid was dried under high vacuum

Sources & evidence

ORD record
ord-85f8a1757b014981b11a6044769be523
Source dataset
uspto-grants-2010_07
Patent number
US07759344B2

Reaction notes

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