Potassium Phosphate, Tribasic → 6-(3-Methyl-3'-(trifluoromethyl)biphenyl-2-yl)-3-morpholinoquinolin-2-amine

HRID 1028984Notes

Reaction equation

HRID 1028984 reaction equation
[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[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=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+]>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH3:34][C:33]1[C:28]([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:29]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:42])([F:43])[F:44])[CH:36]=2)[CH:30]=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673259062-Bromo-3-methyl-3'-(trifluoromethyl)biphenylHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 533291756-(3-Methyl-3'-(trifluoromethyl)biphenyl-2-yl)-3-morpholinoquinolin-2-amine

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of 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), 2-bromo-3-methyl-3′-(trifluoromethyl)biphenyl (66.5 mg, 0.211 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (13.42 mg, 0.028 mmol), potassium phosphate (90 mg, 0.422 mmol) and PdCl2(dppf)-CH2Cl2 adduct (5.15 mg, 7.04 mmol) in ethanol (1206 μL)/water (201 μL) was heated in a sealed tube in the microwave at 140° C. for 20 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 0-70% (10% MeOH/DCM)/DCM to afford 6-(3-methyl-3′-(trifluoromethyl)biphenyl-2-yl)-3-morpholinoquinolin-2-amine MS (ESI, pos. ion) m/z: 464 (M+1).

Workup

  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 0-70% (10% MeOH/DCM)/DCM

Sources & evidence

ORD record
ord-4e6d70919784433a958a4e102c2871d4
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

Loading…