Sodium Carbonate → HCID 66750623, Verbindung

HRID 75464Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 75464
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][CH:9]=2)=[O:6])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[Na+].[Na+].[CH:29]12[N:36]([C:37]3[N:42]=[C:41](Cl)[N:40]=[C:39]([CH2:44][N:45]([CH3:47])[CH3:46])[CH:38]=3)[CH:33]([CH2:34][CH2:35]1)[CH2:32][O:31][CH2:30]2>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:33]12[N:36]([C:37]3[CH:38]=[C:39]([CH2:44][N:45]([CH3:47])[CH3:46])[N:40]=[C:41]([C:11]4[CH:10]=[CH:9][C:8]([NH:7][C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)=[O:6])=[CH:13][CH:12]=4)[N:42]=3)[CH:29]([CH2:35][CH2:34]1)[CH2:30][O:31][CH2:32]2

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 866659081-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine

Produkt 1

HCID 66750623HCID 66750623, VerbindungAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A microwave vial was charged with a solution of 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.496 mmol) in DME (3 ml). Sodium carbonate (2M in water, 0.530 ml, 1.061 mmol), tetrakis(triphenylphosphine)palladium(0) (0.025 g, 0.021 mmol), and 1-(6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-2-chloropyrimidin-4-yl)-N,N-dimethylmethanamine (0.100 g, 0.354 mmol) were added and the resulting solution was sparged with nitrogen for 5 minutes and then heated to 100° C. for 90 minutes via microwave. The vessel was then cooled to room temperature and the reaction mixture was filtered through Celite™. The filter cake was washed with ethyl acetate and the filtrate was washed with saturated sodium chloride and concentrated under reduced pressure to provide a brown oil. The crude product was added to a HPLC column and was eluted with 5-100% acetonitrile in water (0.05% TFA buffer) to provide the mono-TFA salt of 1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((dimethylamino)methyl)pyrimidin-2-yl)phenyl)-3-cyclopropylurea (0.073 g, 49%) as a light yellow solid. MS; 423.2, M+H.

Aufarbeitung

  1. customthe resulting solution was sparged with nitrogen for 5 minutes
  2. temperatureThe vessel was then cooled to room temperature
  3. filtrationthe reaction mixture was filtered through Celite™
  4. washThe filter cake was washed with ethyl acetate
  5. washthe filtrate was washed with saturated sodium chloride
  6. concentrationconcentrated under reduced pressure
  7. customto provide a brown oil
  8. washwas eluted with 5-100% acetonitrile in water (0.05% TFA buffer)

Quellen und Nachweise

ORD-Eintrag
ord-128dc14b2f06485cbc06d55460ff4f97
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835429B2

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