Cesium carbonate → 5-Bromo-3-(5-((3R,5S)-3,5-dimethylmorpholine-4-carbonyl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 1022207Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1022207
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[C@@H:15]([CH3:16])[CH2:14][O:13][CH2:12][C@H:11]2[CH3:17])=[O:9])=[CH:4][CH:3]=1.Br[C:19]1[C:20](=[O:27])[N:21]([CH3:26])[CH:22]=[C:23]([Br:25])[CH:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:25][C:23]1[CH:24]=[C:19]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([N:10]3[C@@H:15]([CH3:16])[CH2:14][O:13][CH2:12][C@H:11]3[CH3:17])=[O:9])=[CH:6][N:7]=2)[C:20](=[O:27])[N:21]([CH3:26])[CH:22]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 86684570(6-Aminopyridin-3-yl)((3R,5S)-3,5-dimethylmorpholino)methanone

Produkt 1

HCID 866845715-Bromo-3-(5-((3R,5S)-3,5-dimethylmorpholine-4-carbonyl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-oneAusbeute 66,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 320a (160 mg, 1.0 eq., 0.68 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (273 mg, 1.5 eq., 1.02 mmol), Pd2(dba)3 (64 mg, 0.1 eq., 0.070 mmol), Xantphos (79 mg, 0.2 eq., 0.14 mmol), Cs2CO3 (444 mg, 2.0 eq., 1.36 mmol), and dioxane (20 mL). After three cycles of vacuum/nitrogen flush, the mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with ethyl acetate to afford 320b (190 mg, 66%) as a yellow solid. MS-ESI: [M+H]+ 420.8.

Aufarbeitung

  1. customA 50-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/nitrogen flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-a8d8cb2de2334320aebb2d8a69c81f7c
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716274B2

Notizen zur Reaktion

Wird geladen…