Water → HCID 67977259, compound

HRID 468846Notes

Reaction equation

HRID 468846 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[NH:8][C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])=[CH:6][C:5]2=[O:19].[CH:20]1([C:23]([NH2:25])=[O:24])[CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.[Cl-].[Na+].O>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:7]1[NH:8][C:9]2[C:4]([C:5](=[O:19])[CH:6]=1)=[CH:3][C:2]([NH:25][C:23]([CH:20]1[CH2:22][CH2:21]1)=[O:24])=[N:11][CH:10]=2

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 80376Cyclopropanecarboxamide2×HCID 866749476-chloro-2-(2-chlorophenyl)-1,7-naphthyridin-4(1H)-one

Product 1

HCID 67977259HCID 67977259, compoundYield 6.2%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 6-chloro-2-(2-chlorophenyl)-1,7-naphthyridin-4(1H)-one (29.2 mg, 100 μmol), cyclopropanecarboxamide (17.1 mg, 200 μmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoeth yl)phenyl]palladium(II) (8.0 mg, 10 μmol), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (5.4 mg, 10 μmol), and cesium carbonate (98.0 mg, 301 μmol) in 1,4-dioxane (5.0 mL) was heated to reflux for 4 hours. Further portions of cyclopropanecarboxamide (17.1 mg, 200 μmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoeth yl)phenyl]palladium(II) (8.0 mg, 10 μmol) and 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (5.4 mg, 10 μmol) were added and the mixture heated to reflux for 16 hours. The cooled mixture was treated with water and brine and extracted with ethyl acetate, and the separated organic phase washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid) to afford the title compound as a white solid (2.1 mg, 6.2%). LCMS (Method E): RT=3.715 min, M+H+=340.0 & 342.0.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 hours
  3. temperaturethe mixture heated
  4. temperatureto reflux for 16 hours
  5. extractionextracted with ethyl acetate
  6. washthe separated organic phase washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid)

Sources & evidence

ORD record
ord-ec2c039f7a5f43f89bb96ebc222bfb74
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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