Potassium Carbonate → HCID 57594300, Verbindung

HRID 1714571Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1714571
Br[C:2]1[C:3]2[N:4]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][C@H:18]([NH:22][C:23](=[O:36])[C:24]4[CH:29]=[CH:28][C:27]([O:30][CH:31]([CH3:33])[CH3:32])=[C:26]([C:34]#[N:35])[CH:25]=4)[CH2:19][CH2:20][OH:21])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:37][C:38]1[C:42](B(O)O)=[C:41]([CH3:46])[O:40][N:39]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:34]([C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][C:27]=1[O:30][CH:31]([CH3:32])[CH3:33])[C:23]([NH:22][C@@H:18]([CH2:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:3]3[C:2]([C:42]4[C:38]([CH3:37])=[N:39][O:40][C:41]=4[CH3:46])=[CH:7][CH:6]=[CH:5][N:4]3[CH:8]=2)=[CH:12][CH:13]=1)[CH2:19][CH2:20][OH:21])=[O:36])#[N:35]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 11699582HCID 11699582, Verbindung

Produkt 1

HCID 57594300HCID 57594300, VerbindungAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of N-((1S)-1-{[4-(8-bromoimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (200 mg, 0.366 mmol) in dry DMF (2 mL) were added 3,5-dimethyl-isoxazole-4-boronic acid (63 mg, 0.439 mmol), tetrakistriphenylphosphine palladium(0) (21 mg, 0.018 mmol) and 2.0M aqueous K2CO3 (0.46 mL) successively at rt. The reaction mixture was purged with argon and heated to 100° C., stirred for 22 h, cooled to rt, filtered and purified directly by reverse phase HPLC (MeCN/H2O with 0.1% TFA). The clean fractions were adjusted to pH ˜8 with saturated aqueous NaHCO3 and extracted with 3% MeOH/EtOAc (3×30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give 45 mg (22%) of the title compound as an off-white solid. LC/MS (ES) m/e 564.2 (M+H)+.

Aufarbeitung

  1. customThe reaction mixture was purged with argon
  2. temperaturecooled to rt
  3. filtrationfiltered
  4. custompurified directly by reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  5. extractionextracted with 3% MeOH/EtOAc (3×30 mL)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-92f38c1f2fd242008f8bd81f33bc4ab0
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07795448B2

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