Morpholine → (5'-Isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

HRID 604154Notes

Reaction equation

HRID 604154 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[C:20]2[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=2[O:29][CH3:30])=[N:6][CH:7]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:26]([C:24]1[CH:23]=[CH:22][C:21]([O:29][CH3:30])=[C:20]([C:11]2[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][C:10]=2[CH2:9][NH:8][C:5]2[N:4]=[CH:3][C:2]([N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[CH:7][N:6]=2)[CH:25]=1)([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 67087228(5-Bromo-pyrimidin-2-yl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine

Product 1

HCID 67087545(5'-Isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

(5-Bromo-pyrimidin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (3.30 g) is dissolved in toluene (30 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (1.26 g), 2-(di-tert-butylphosphino)biphenyl (1.23 g), morpholine (2.4 ml) and sodium tert-butoxide (1.32 g) and the mixture is degassed under reduced pressure and stirred under nitrogen flow at 50° C. overnight. To the reaction mixture is added a saturated brine, and extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:1) to give (5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (1.11 g). MS (m/z): 487 [M+H]+

Workup

  1. customthe mixture is degassed under reduced pressure
  2. additionTo the reaction mixture is added a saturated brine
  3. extractionextracted with ethyl acetate
  4. washThe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:1)

Sources & evidence

ORD record
ord-81edafebbe234675862ebe5ed88a10d3
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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