Potassium Phosphate, Tribasic → 6-(2-(3,4-Dihydroisoquinolin-1-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

HRID 1028943

Reaktionsgleichung

Reaktionsgleichung von HRID 1028943
[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]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37][N:36]=1.P([O-])([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>[C:35]1([C:29]2[CH:30]=[CH:31][CH:32]=[C:33]([CH3:34])[C:28]=2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[C:8]([NH2:26])[C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[CH:16]3)[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37][N:36]=1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673246531-(2-Bromo-3-methylphenyl)-3,4-dihydroisoquinolineHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Produkt 1

HCID 673247536-(2-(3,4-Dihydroisoquinolin-1-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

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 (0.18 g, 0.50 mmol), 1-(2-bromo-3-methylphenyl)-3,4-dihydroisoquinoline (0.10 g, 0.33 mmol), potassium phosphate (0.354 g, 1.67 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.032 g, 0.067 mmol) and Pd2 dba3 (0.015 g, 0.017 mmol) were treated with dioxane (2.22 mL) and Water (1.11 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 layers 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 6-(2-(3,4-dihydroisoquinolin-1-yl)-6-methylphenyl)-3-morpholinoquinolin-2-amine MS (ESI, pos. ion) m/z: 449 (M+1).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. customthen partitioned between EtOAc and water
  3. washThe organic layers 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-22cbe4354802463cb1fced1fe3a67e7e
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735384B2

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