Morpholine → 8-Chloro-N-(2,5-di-4-morpholinylphenyl)-2,3-dimethyl-4-quinolinamine

HRID 1431300Notes

Reaction equation

HRID 1431300 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[C:6]([NH:8][C:9]2[C:18]3[C:13](=[C:14]([Cl:19])[CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([CH3:20])[C:10]=2[CH3:21])[CH:7]=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[N:12]=[C:11]([CH3:20])[C:10]([CH3:21])=[C:9]2[NH:8][C:6]1[CH:7]=[C:2]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:3]=[CH:4][C:5]=1[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59631074N-(5-Bromo-2-morpholinophenyl)-8-chloro-2,3-dimethylquinolin-4-amine

Product 1

HCID 596314088-Chloro-N-(2,5-di-4-morpholinylphenyl)-2,3-dimethyl-4-quinolinamine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

In a teflon-capped vial, a mixture of N-(5-bromo-2-morpholinophenyl)-8-chloro-2,3-dimethylquinolin-4-amine (75 mg, 168 μmol), morpholine (0.02 mL, 252 μmol), Pd2dba3 (15 mg, 17 μmol), X-Phos (8 mg, 17 μmol) and cesium carbonate (82 mg, 252 μmol) in 1,4-dioxane (4.00 mL) was purged with nitrogen, capped and heated in a 120° C. oil bath for 72 h. The reaction mixture was partitioned between 25 mL EtOAc and 25 mL water. The organic separation was stirred over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford and orange oil. The product was purified by preparative reversed-phase HPLC to afford a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 7.83 (2H, dd, J=11.7, 7.8 Hz), 7.34-7.44 (1H, m), 7.09-7.18 (2H, m), 6.90 (1H, dd, J=8.8, 2.5 Hz), 6.60 (1H, d, J=2.7 Hz), 3.76 (8H, ddd, J=17.8, 4.7, 4.5 Hz), 2.97-3.16 (8H, m), 2.92 (3H, s), 2.24 (3H, s). Mass Spectrum (ESI) m/e=453.1 (M+1).

Workup

  1. customwas purged with nitrogen
  2. customcapped
  3. customThe reaction mixture was partitioned between 25 mL EtOAc and 25 mL water
  4. customThe organic separation
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customto afford
  8. customThe product was purified by preparative reversed-phase HPLC
  9. customto afford a yellow oil

Sources & evidence

ORD record
ord-f79dc70f2fc647c7b8c636e31446fef8
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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