Cesium carbonate → ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate

HRID 226395Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 226395
Cl[C:2]1[N:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=1.[NH2:15][C@H:16]1[CH2:21][N:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:19](=[O:30])[CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:22][N:20]1[C:19](=[O:30])[CH2:18][CH2:17][C@@H:16]([NH:15][C:2]2[N:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=2)[CH2:21]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68960470(5R)-5-amino-1-(benzyloxy)-2-piperidinoneHCID 86603667Ethyl (2E)-3-(5-chloro-2-pyrazinyl)acrylate

Produkt 1

HCID 86603704ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylateAusbeute 43,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

Ethyl (2E)-3-(5-chloro-2-Pyrazinyl)acrylate (250 mg, 1.18 mmol) and (5R)-5-amino-1-(benzyloxy)-2-piperidinone (388 mg, 1.86 mmol) were combined in 1,4-dioxane (4 mL) at ambient temperature. To this solution were added palladium(II) acetate (18 mg, 0.8 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (46 mg, 0.1 mmol) at the same temperature and the mixture was stirred for 5 minutes. To the resulting mixture was added cesium carbonate (536 mg, 1.86 mmol) and the mixture was heated at 95° C. for 24 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between water and EtOAc. The organic layer was separated, washed water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (CHCl3/methanol=95/1) to give ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate (202 mg, 43%) as an amorphous solid.

Aufarbeitung

  1. customThe reaction mixture was evaporated in vacuo
  2. customthe residue was partitioned between water and EtOAc
  3. customThe organic layer was separated
  4. washwashed water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (CHCl3/methanol=95/1)

Quellen und Nachweise

ORD-Eintrag
ord-d9df0d9aa507486b9839f949e752fad9
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557127B2

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