Cesium carbonate → (S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398308Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398308
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH:16]3[CH2:18][CH2:17]3)[C:6]=2[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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:56]([NH:63][C@H:64]([CH2:69][OH:70])[CH2:65][CH:66]([CH3:68])[CH3:67])([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:16]1([N:7]2[C:6]3[CH:19]=[C:2]([O:70][CH2:69][C@@H:64]([NH:63][C:56](=[O:57])[O:58][C:59]([CH3:60])([CH3:62])[CH3:61])[CH2:65][CH:66]([CH3:68])[CH3:67])[CH:3]=[CH:4][C:5]=3[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8]2=[O:15])[CH2:18][CH2:17]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 867103158-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5(6H)-one

Produkt 1

HCID 86710316(S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateAusbeute 26,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution 8-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5(6H)-one (200 mg, 0.739 mmol) in toluene (2 mL) at room temperature was added cesium carbonate (361 mg, 1.108 mmol) and di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (188 mg, 0.443 mmol) and the mixture was degassed with nitrogen for 5 min. The mixture was then treated with N-Boc-L-leucinol (477 mg, 2.216 mmol) followed by palladium(II)acetate (49.8 mg, 0.222 mmol) and degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. After overnight stirring the reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford crude product which was purified by combi flash (ethyl acetate and petroleum ether) to afford (S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.195 mmol, 26% yield) as an off-white solid. LC/MS (ESI) m/e 452.2 [(M+H)+, calcd for C26H34N3O4 452.3]; LC/MS retention time (method C): tR=2.11 min.

Aufarbeitung

  1. customthe mixture was degassed with nitrogen for 5 min
  2. customdegassed for another 10 min
  3. customThe reaction mixture was sealed
  4. temperaturewas cooled to room temperature
  5. filtrationfiltered through diatomaceous earth (Celite®)
  6. washThe bed was washed with ethyl acetate
  7. concentrationthe combined filtrate was concentrated under reduced pressure
  8. customto afford crude product which
  9. customwas purified by combi flash (ethyl acetate and petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-96b6fdcbe13b4628abd8616705a51cf8
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901305B2

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