Cesium carbonate → (S)-tert-butyl (1-((9-(4-fluorophenyl)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 1398407Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398407
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:33][C:34]1[CH:39]=[CH:38][C:37]([C:2]2[C:17]([O:18][CH2:19][C@@H:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:31])[CH3:30])[CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][C:5]3[N:6]([CH3:15])[C:7](=[O:14])[C:8]4[C:13]([C:4]=3[CH:3]=2)=[CH:12][CH:11]=[N:10][CH:9]=4)=[CH:36][CH:35]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Produkt 1

HCID 86710395(S)-tert-butyl (1-((9-(4-fluorophenyl)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateAusbeute 31 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

(S)-tert-Butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (150 mg, 0.297 mmol) (prepared as described in Example 3, Part A) 4-fluorophenylboronic acid (49.9 mg, 0.357 mmol), Cs2CO3 (291 mg, 0.892 mmol) and PdCl2(dppf)-CH2Cl2 adduct (12.14 mg, 0.015 mmol) in 1,4-dioxane (8 mL) and water (0.4 mL) was degassed with nitrogen gas for 5 min then heated at 80° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was taken up in dichloromethane (10 mL) and water (8 mL). The organic layer was separated, dried with sodium sulfate, filtered and concentrated under reduced pressure to afford (S)-tert-butyl (1-((9-(4-fluorophenyl)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.13 g, 0.09 mmol, 31% yield) as a brown gum. The material was carried forward without further purification. LC/MS, (ESI) m/z 520.4 [(M+H)+, calcd for C30H35FN3O4 520.25]; LC/MS retention time (method D): tR=1.08 min.

Aufarbeitung

  1. customwas degassed with nitrogen gas for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe organic layer was separated
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-89efeb3ffff44bc8ac03640751395763
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901305B2

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