Cesium carbonate → 6-(4-nitro-1H-pyrazol-1-yl)isoquinoline

HRID 598875Notes

Reaction equation

HRID 598875 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].Br[C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[N:15][CH:14]=[CH:13]2.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N+:1]([C:4]1[CH:5]=[N:6][N:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[N:15][CH:14]=[CH:13]3)[CH:8]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 163764-nitro-1H-pyrazoleHCID 3136816-BromoisoquinolineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane

Product 1

HCID 670626806-(4-nitro-1H-pyrazol-1-yl)isoquinolineYield 86.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-nitro-1H-pyrazole (510 mg, 4.51 mmol), 6-bromoisoquinoline (375 mg, 1.80 mmol) (commercially available from Gateway Chemical Technology, Inc.), tris(dibenzylideneacetone)dipalladium (0) (165 mg, 180 μmol), 2-ditert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (153 mg, 360 μmol), and cesium carbonate (1.76 g, 5.41 mmol) in dioxane (4 mL) was heated in a sealed vial at 105° C. for 6 hours. The mixture was cooled to ambient temperature and partitioned between DCM (30 mL) and H2O (30 mL). The layers were separated, and the aqueous layer was extracted with DCM (2×20 mL) and 10% MeOH/DCM (30 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow solid was dissolved in DCM, evaporated onto silica gel, and purified by flash chromatography (Biotage Si 40+M, 20% to 50% acetone/hexanes) to provide 6-(4-nitro-1H-pyrazol-1-yl)isoquinoline (374 mg, 86% yield) as a white solid. LCMS (API-ES) m/z (%): 241.1 (100%, M++H); 1H NMR (300 MHz, CDCl3) δ ppm 7.76 (d, J=5.8 Hz, 1H), 8.01 (dd, J=8.8, 2.2 Hz, 1H), 8.14-8.23 (m, 2H), 8.36 (s, 1H), 8.65 (d, J=5.8 Hz, 1H), 8.83 (s, 1H), 9.34 (s, 1H).

Workup

  1. custompartitioned between DCM (30 mL) and H2O (30 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with DCM (2×20 mL) and 10% MeOH/DCM (30 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting yellow solid was dissolved in DCM
  7. customevaporated onto silica gel
  8. custompurified by flash chromatography (Biotage Si 40+M, 20% to 50% acetone/hexanes)

Sources & evidence

ORD record
ord-91bf197eaad04eb9bac1fd8e61f7945d
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

Loading…