Potassium Phosphate, Tribasic → 6-(2-((2-Chloro-5-(trifluoromethyl)phenoxy)methyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

HRID 1028982

Reaktionsgleichung

Reaktionsgleichung von HRID 1028982
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=1[Cl:21].[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:29]([NH2:47])=[N:30][C:31]3[C:36]([CH:37]=2)=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=3)[CH2:24][CH2:23]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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>[Cl:21][C:12]1[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=1[O:10][CH2:9][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=1[C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[N:30]=[C:29]([NH2:47])[C:28]([N:25]1[CH2:24][CH2:23][O:22][CH2:27][CH2:26]1)=[CH:37]2

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673247022-Bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzeneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Produkt 1

HCID 533291746-(2-((2-Chloro-5-(trifluoromethyl)phenoxy)methyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Versuchsvorschrift

A degassed solution of 2-bromo-1-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-3-methylbenzene (64.1 mg, 0.169 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (50 mg, 0.141 mmol, prepared as in Example 2, Step 1-2), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (13.42 mg, 0.028 mmol), potassium phosphate (149 mg, 0.704 mmol) and Pd2(dba)3 (6.44 mg, 7.04 μmol) in dioxane (0.94 mL)/water (0.47 mL) was heated in a sealed tube in the microwave at 140° C. for 15 min. The reaction was then quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was then washed with water and brine (3× ea.), dried over Na2SO4 and concentrated in vacuo to remove the solvent. The crude material was purified by column chromatography with 0-100% (10% NH3 in MeOH/DCM)/DCM to afford 6-(2-((2-chloro-5-(trifluoromethyl)phenoxy)methyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine. MS (ESI, pos. ion) m/z: 528 (M+1).

Aufarbeitung

  1. customThe reaction was then quenched with water
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe organic layer was then washed with water and brine (3× ea.)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto remove the solvent
  7. customThe crude material was purified by column chromatography with 0-100% (10% NH3 in MeOH/DCM)/DCM

Quellen und Nachweise

ORD-Eintrag
ord-04c8d4efde624b29bb29d54a8231cfed
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735384B2

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