Ethyl Acetate → HCID 178435467, compound

HRID 1256215Notes

Reaction equation

HRID 1256215 reaction equation
[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])[C:9]3[CH:10]=[C:11](I)[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1.[CH3:24][CH2:25]OC(C)=O>CN(C=O)C.[F-].[K+]>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])[C:9]3[CH:10]=[C:11]([CH:24]=[CH2:25])[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 178505721HCID 178505721, compound

Product 1

HCID 178435467HCID 178435467, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
100 °C

Procedure

A 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 2.22 g of 3-bromo-5-(2,6-difluorophenyl)-7-iodo-1H-pyrazolo[4,3-c]isoquinoline in 11 ml of DMF. After argon has been bubbled through the mixture for 10 min, 1.47 ml of tributylvinylstannane and 481 mg of bis(triphenylphosphene)palladium(II) dichloride are added. The mixture is heated at 100° C. for 1 h and then after cooling is evaporated to dryness under vacuum. This gives an oil which is taken up in 350 ml of AcOEt and 300 ml of 20% aqueous KF solution. The mixture is stirred at RT for 30 min and then the suspension is filtered on a glass frit bearing a bed of Clarcel Flo. The organic phase is extracted with AcOEt and then washed with saturated aqueous NaCl solution, dried over MgSO4 and evaporated to dryness under RP. This gives 3.1 g of a crude product, which is purified by chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (95/5 by vol.), to give 1.44 g of 3-bromo-5-(2,6-difluorophenyl)-7-vinyl-1H-pyrazolo[4,3-c]isoquinoline (light yellow solid). MS (E/I): m/z=386 (M+); 1H NMR: 5.43 (d, J=11.2 Hz, 1H); 6.00 (d, J=17.6 Hz, 1H); 6.92 (dd, J=17.6, 11.2 Hz, 1H); 7.37 (t, J=7.9 Hz, 2H); 7.65 (broad s, 1H); 7.73 (m, 1H); 8.33 (dd, J=8.8, 1.5 Hz, 1H); 8.51 (d, J=8.8 Hz, 1H); 14.59 (broad m, 1H).

Workup

  1. customA 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. customAfter argon has been bubbled through the mixture for 10 min
  3. addition1.47 ml of tributylvinylstannane and 481 mg of bis(triphenylphosphene)palladium(II) dichloride are added
  4. temperatureafter cooling
  5. customis evaporated to dryness under vacuum
  6. customThis gives an oil which
  7. filtrationthe suspension is filtered on a glass frit
  8. extractionThe organic phase is extracted with AcOEt
  9. washwashed with saturated aqueous NaCl solution
  10. dry with materialdried over MgSO4
  11. customevaporated to dryness under RP
  12. customThis gives 3.1 g of a crude product, which is purified by chromatography on silica gel (20-45 μm)
  13. washeluting with a mixture of DCM and methanol (95/5 by vol.)

Sources & evidence

ORD record
ord-becc18a5b94a4ae4abc888c48be6049a
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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