Selectfluor → HCID 22341791, compound

HRID 585017Notes

Reaction equation

HRID 585017 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]2[C:22](=[O:31])[NH:23][C:24]4[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:15]3)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[B-](F)(F)(F)[F:33].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[F:33][C:15]1[C:14]2[C:18](=[CH:19][CH:20]=[C:12]([CH2:11][N:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH2:6][CH2:7]3)[CH:13]=2)[NH:17][C:16]=1[C:21]1[C:22](=[O:31])[NH:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 9849987335649-90-6

Product 1

HCID 22341791HCID 22341791, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

3-(5-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H)-one (3-1, 60 mg, 1.37 mmol) was dissolved in 5 mL of anhydrous dimethylsolfoxide and diluted with 5 mL of anhydrous acetonitrile. The solution was cooled to 0° C., and the fluorinating reagent, 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate, 3-2 (0.25 equiv., 12 mg, 0.03 mmol) was added. After addition, the ice bath was removed, and the reaction stirred at room temperature for 30 minutes. 3-2 was continually added in this fashion until half of the starting material was consumed. At which point, the reaction was diluted with ethyl acetate (150 mL) and partitioned with water (25 mL). The two layers were separated, and the organic layer was washed several times with water. The organic layer was condensed under vacuum. The crude residue was purified by reverse phase HPLC (5-95% ACN/H2O-40 minutes). The pure fractions were combined and volatiles were removed under reduced pressure. The resulting solution was partitioned with ethyl acetate (200 mL) and washed with 1 N NaOH (15 mL) and brine. The organic layer was dried with Na2SO4, filtered and condensed under vacuum. The resulting pure product was isolated as yellow solid; 1H NMR (500 MHz, DMSO-d6) δ 12.3 (s, 1H), 11.3 (s, 1H), 8.47 (s, 1H), 7.83 (d, 1H, J=7.8 Hz), 7.58-7.52 (m, 2H), 7.46 (s, 1H), 7.39 (d, 1H, J=8.3 Hz), 7.26 (t, 1H, J=7.8 Hz), 7.13 (d, 1H, J=8.5 Hz), 3.60 (s, H), 3.11 (m, 4H), 2.87 (s, 3H), 2.48 (m, 4H).

Workup

  1. additionAfter addition
  2. customthe ice bath was removed
  3. addition3-2 was continually added in this fashion until half of the starting material
  4. customwas consumed
  5. additionAt which point, the reaction was diluted with ethyl acetate (150 mL)
  6. custompartitioned with water (25 mL)
  7. customThe two layers were separated
  8. washthe organic layer was washed several times with water
  9. customcondensed under vacuum
  10. customThe crude residue was purified by reverse phase HPLC (5-95% ACN/H2O-40 minutes)
  11. customvolatiles were removed under reduced pressure
  12. customThe resulting solution was partitioned with ethyl acetate (200 mL)
  13. washwashed with 1 N NaOH (15 mL) and brine
  14. dry with materialThe organic layer was dried with Na2SO4
  15. filtrationfiltered
  16. customcondensed under vacuum
  17. customThe resulting pure product was isolated as yellow solid

Sources & evidence

ORD record
ord-48bb923164ac4473adf95e7897f66034
Source dataset
uspto-grants-2005_08
Patent number
US06927293B2

Reaction notes

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