Potassium Phosphate, Tribasic → 2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylbenzonitrile

HRID 1028958

Reaction equation

HRID 1028958 reaction equation
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.Br[C:44]1[C:51]([CH3:52])=[CH:50][CH:49]=[CH:48][C:45]=1[C:46]#[N:47].[O:53]1[CH2:58][CH2:57][N:56]([C:59]2[C:60]([NH2:78])=[N:61][C:62]3[C:67]([CH:68]=2)=[CH:66][C:65](B2OC(C)(C)C(C)(C)O2)=[CH:64][CH:63]=3)[CH2:55][CH2:54]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[NH2:78][C:60]1[C:59]([N:56]2[CH2:57][CH2:58][O:53][CH2:54][CH2:55]2)=[CH:68][C:67]2[C:62](=[CH:63][CH:64]=[C:65]([C:44]3[C:51]([CH3:52])=[CH:50][CH:49]=[CH:48][C:45]=3[C:46]#[N:47])[CH:66]=2)[N:61]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 154691152-Bromo-3-methylbenzonitrileHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 673450552-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylbenzonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of potassium phosphate (5.98 g, 28.2 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.54 g, 1.13 mmol), Pd2(dba)3 (0.26 g, 0.28 mmol), 2-bromo-3-methylbenzonitrile (2.21 g, 11.26 mmol) and 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (2.00 g, 5.63 mmol, prepared as in Example 2, Step 1-2) was added dioxane (50.0 mL) and water (25.0 mL). The mixture was heated to 140° C. for 10 min. The reaction mixture was allowed to cool to RT, filtered and then partitioned between EtOAc and water. The organic layer was washed with water and brine, and concentrated. The residue was diluted with EtOAc and then filtered. The solid was dried in air to afford 2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylbenzonitrile as a light brown solid.

Workup

  1. temperatureto cool to RT
  2. filtrationfiltered
  3. custompartitioned between EtOAc and water
  4. washThe organic layer was washed with water and brine
  5. concentrationconcentrated
  6. additionThe residue was diluted with EtOAc
  7. filtrationfiltered
  8. customThe solid was dried in air

Sources & evidence

ORD record
ord-7f6f23c9a4ae497b955691427325cfcf
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Linked notes

Loading…