Cesium carbonate → tert-butyl((3S)-2-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5-methylhexan-3-yl)carbamate

HRID 1398383Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398383
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.[OH:19][CH:20]([C@@H:22]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:23][CH:24]([CH3:26])[CH3:25])[CH3:21].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>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:30]([O:29][C:28](=[O:34])[NH:27][C@@H:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[CH:20]([O:19][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1)[CH3:21])([CH3:32])([CH3:33])[CH3:31]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 56634861tert-butyl ((3S)-2-hydroxy-5-methylhexan-3-yl)carbamateHCID 867103378-Chloro-4,6-dimethyl-5H,6H-benzo[c]2,7-naphthyridin-5-one

Produkt 1

HCID 89957265tert-butyl((3S)-2-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5-methylhexan-3-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.05 g, 0.193 mol), tert-butyl ((3S)-2-hydroxy-5-methylhexan-3-yl)carbamate (0.067 g, 0.290 mmol), Cs2CO3 (0.315 g, 0.966 mol), 2-di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (8.21 mg, 0.019 mol) and Pd(OAc)2 (2.60 mg, 0.012 mol) were taken in Toluene (2 mL) and heated overnight at 90° C. After cooling the reaction mixture was concentrated, then diluted with ethyl acetate and water. Ethyl acetate layer was collected, dried over Na2SO4, filtered and concentrated which afforded tert-butyl((3S)-2-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5-methylhexan-3-yl)carbamate, (70 mg, 0.154 mmol, 80% crude yield) as brown solid. The crude product was used for next step without further purification. LC/MS (ESI) m/e 454.2 [(M+H)+, calcd for C26H36N3O4, 454.3]; LC/MS retention time (method D): tR=0.91 min.

Aufarbeitung

  1. temperatureAfter cooling the reaction mixture
  2. concentrationwas concentrated
  3. additiondiluted with ethyl acetate and water
  4. customEthyl acetate layer was collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated which

Quellen und Nachweise

ORD-Eintrag
ord-09c514ffe5d0433f858845629d4c1510
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901305B2

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