1,4-Dioxane → (2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone

HRID 1028939

Reaktionsgleichung

Reaktionsgleichung von HRID 1028939
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[C:43]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[CH3:51])=[O:44].[O:52]1[CH2:57][CH2:56][N:55]([C:58]2[C:59]([NH2:77])=[N:60][C:61]3[C:66]([CH:67]=2)=[CH:65][C:64](B2OC(C)(C)C(C)(C)O2)=[CH:63][CH:62]=3)[CH2:54][CH2:53]1.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].O>[NH2:77][C:59]1[C:58]([N:55]2[CH2:56][CH2:57][O:52][CH2:53][CH2:54]2)=[CH:67][C:66]2[C:61](=[CH:62][CH:63]=[C:64]([C:36]3[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=3[C:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])=[O:44])[CH:65]=2)[N:60]=1

Komponenten

7

Edukt 4

HCID 312751,4-DioxaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67326275(2-Bromo-3-methylphenyl)(o-tolyl)methanoneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Produkt 1

HCID 67325352(2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.013 g, 0.028 mmol), (2-bromo-3-methylphenyl)(o-tolyl)methanone (0.16 g, 0.563 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.050 g, 0.141 mmol), Pd2(dba)3 (6.44 mg, 7.04 μmol) were treated with dioxane (0.94 mL) and water (0.47 mL) in a medium-sized Smith synthesizer vial. The mixture was heated to 140° C. for 12 min in a microwave reactor. The reaction mixture was filtered then partitioned between EtOAc and water. The organic layer was washed with water and brine and then concentrated in vacuo. The crude product was purified first by column chromatography (1-10% MeOH:DCM) and then by HPLC (10-90% CH3CN/H2O; TFA modifier). A single fraction was treated with NH4OH, concentrated, filtered and air-dried to afford (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone. MS (ESI, pos. ion) m/z: 438 (M+1).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. customthen partitioned between EtOAc and water
  3. washThe organic layer was washed with water and brine
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified first by column chromatography (1-10% MeOH:DCM)
  6. additionA single fraction was treated with NH4OH
  7. concentrationconcentrated
  8. filtrationfiltered
  9. customair-dried

Quellen und Nachweise

ORD-Eintrag
ord-55607327fa5240309e549266d24cbacb
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735384B2

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