Potassium Phosphate, Tribasic → (2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(tetrahydrofuran-2-yl)methanone

HRID 1028947

Reaktionsgleichung

Reaktionsgleichung von HRID 1028947
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([NH2:26])=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][CH:11]=3)[CH2:3][CH2:2]1.Br[C:28]1[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:29]=1[C:35]([CH:37]1[CH2:41][CH2:40][CH2:39][O:38]1)=[O:36].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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.O1CCOCC1>[NH2:26][C:8]1[C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:28]3[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:29]=3[C:35]([CH:37]3[CH2:41][CH2:40][CH2:39][O:38]3)=[O:36])[CH:14]=2)[N:9]=1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67325377(2-Bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanoneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Produkt 1

HCID 67379958(2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(tetrahydrofuran-2-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.099 g, 0.279 mmol), (2-bromo-3-methylphenyl)(tetrahydrofuran-2-yl)methanone (0.050 g, 0.186 mmol), potassium phosphate tribasic (0.077 mL, 0.929 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.018 g, 0.037 mmol), and Pd2(dba)3 (8.51 mg, 9.29 μmol) were treated with dioxane (1.2 mL) and water (0.62 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, organics were washed with water and brine and then concentrated in vacuo. The crude product was purified by silica flash chromatography (1-10% MeOH/DCM) and then by HPLC (10-75% acetonitril/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)(tetrahydrofuran-2-yl)methanone. MS (ESI, pos. ion) m/z: 418 (M+1).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. customthen partitioned between EtOAc and water
  3. washorganics were washed with water and brine
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica flash 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-94361365f92d4f09b0b453564c0b4f34
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735384B2

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