Cesium carbonate → Methyl 3-[[6-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-3-methyl-pyridine-2-carbonyl]amino]-2,4-dimethyl-benzoate

HRID 239964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 239964
Cl[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[C:12]([CH3:22])=[C:13]([CH:18]=[CH:19][C:20]=2[CH3:21])[C:14]([O:16][CH3:17])=[O:15])=[O:9])[C:5]([CH3:23])=[CH:4][CH:3]=1.[C:24]([Si:28]([CH3:38])([CH3:37])[O:29][CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]1)([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[Cs+].[Cs+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.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]>[Si:28]([O:29][CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][N:33]([C:2]2[N:7]=[C:6]([C:8]([NH:10][C:11]3[C:12]([CH3:22])=[C:13]([CH:18]=[CH:19][C:20]=3[CH3:21])[C:14]([O:16][CH3:17])=[O:15])=[O:9])[C:5]([CH3:23])=[CH:4][CH:3]=2)[CH2:32]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:38])[CH3:37]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58992622Tert-butyl-dimethyl-(3-piperidylmethoxy)silaneHCID 86707343Methyl 3-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-2,4-dimethyl-benzoate

Produkt 1

HCID 86707348Methyl 3-[[6-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-piperidyl]-3-methyl-pyridine-2-carbonyl]amino]-2,4-dimethyl-benzoateAusbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of methyl 3-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-2,4-dimethyl-benzoate (0.5 g, 0.0015 mol, see preparation 40), tert-butyl-dimethyl-(3-piperidylmethoxy)silane (0.41 g, 0.0018 mol, see preparation 14) and Cs2CO3 (1.95 g, 0.006 mol) in 1,4-dioxane (20 ml) is added Pd2(dba)3 (0.137 g, 0.00015 mol) followed by S-Phos (0.06 g, 0.00015 mol). The reaction mixture is purged with nitrogen for 5 minutes and then heated at 80° C. After 24 hours, the reaction is cooled to ambient temperature, filtered through Celite™, and washed with EtOAc. The combined filtrates are dried over sodium sulfate, filtered, and concentrated under reduced pressure and purified by flash chromatography (silica gel) using 20% EtOAc in hexane to afford the title compound as a brown semi-solid (0.2 g, 38%). Mass spectrum (m/z): 525.2 (M+1).

Aufarbeitung

  1. customThe reaction mixture is purged with nitrogen for 5 minutes
  2. temperaturethe reaction is cooled to ambient temperature
  3. filtrationfiltered through Celite™
  4. washwashed with EtOAc
  5. dry with materialThe combined filtrates are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by flash chromatography (silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-f9352ba7efe448998a3b3af176d35e5b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642768B2

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