Acetic Acid → HCID 86726861, compound

HRID 924373Notes

Reaction equation

HRID 924373 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([O:25]CC)=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1C=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(O)=O>CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([OH:25])=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([CH2:31][C:30]#[N:29])[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 10796Cesium carbonateHCID 164141804-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazoleHCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 86726861HCID 86726861, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphaneCatalyst

Conditions

Temperature
90 °C

Procedure

To a screw-cap vial equipped with a magnetic stir bar, ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (105.9 mg, 0.2467 mmol), 4-isoxazoleboronic acid pinacol ester (Aldrich, 75.8 mg, 0.389 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (Aldrich, 20.5 mg, 0.0260 mmol) and cesium carbonate (257.9 mg, 0.7915 mmol) were added. The vial was sealed with a Teflon®-lined septum, and then evacuated and backfilled with nitrogen three times. 1,4-Dioxane (2.00 mL) was added via a syringe, followed by deoxygenated water (1.00 mL). The reaction mixture was heated at 90° C. for 2 h and was then allowed to cool to room temperature. After cooling, the reaction mixture was diluted with water (50 mL). AcOH (159 mg, 2.66 mmol) was added to adjust the pH to 5. The mixture was extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM) to give the sub-title compound as a brown solid (46.2 mg, 52%). LCMS calc. for C20H16N3O4 (M+H)+: m/z=362.1. found 362.1.

Workup

  1. customTo a screw-cap vial equipped with a magnetic stir bar
  2. customevacuated
  3. addition1,4-Dioxane (2.00 mL) was added via a syringe
  4. customby deoxygenated water (1.00 mL)
  5. temperatureto cool to room temperature
  6. temperatureAfter cooling
  7. additionthe reaction mixture was diluted with water (50 mL)
  8. extractionThe mixture was extracted with EtOAc (3×50 mL)
  9. extractionThe combined organic extract
  10. washwas washed with brine (100 mL)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-1ca68bba2d0c483785786b5fc2198c71
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

Loading…