Binap, (A+-)- → Tert-butyl 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyrate

HRID 604098Notes

Reaction equation

HRID 604098 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[N:13]([CH2:16][C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=1)[CH2:14][CH3:15].Cl[C:32]1[N:37]=[CH:36][C:35]([O:38][CH2:39][CH2:40][CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[CH:34][N:33]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.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]>[F:30][C:27]([F:28])([F:29])[C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=1)[CH2:16][N:13]([CH2:14][CH3:15])[C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:11])([F:12])[F:10])=[CH:8][C:3]=1[CH2:2][NH:1][C:32]1[N:33]=[CH:34][C:35]([O:38][CH2:39][CH2:40][CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[CH:36][N:37]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 57556051Tert-butyl 4-(2-chloro-pyrimidin-5-yloxy)-butyrateHCID 86626850(2-Aminomethyl-4-trifluoromethyl-phenyl)-(3,5-bis-trifluoromethyl-benzyl)-ethyl-amine

Product 1

HCID 86626851Tert-butyl 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyrateYield 28.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

(2-Aminomethyl-4-trifluoromethyl-phenyl)-(3,5-bis-trifluoromethyl-benzyl)-ethyl-amine (165 mg) is dissolved in toluene (3 ml) and thereto are added tert-butyl 4-(2-chloro-pyrimidin-5-yloxy)-butyrate (202 mg), tris(dibenzylideneacetone)dipalladium(0) (68 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (92 mg) and sodium tert-butoxide (71 mg), and the mixture is stirred under nitrogen flow at 80° C. for 5 hours. To the reaction mixture is added a saturated brine, and the mixture is 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 NH-silica gel column chromatography (hexane:ethyl acetate=7:1) to give tert-butyl 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyrate (73 mg). MS (m/z): 681 [M+H]+

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=7:1)

Sources & evidence

ORD record
ord-ce3681308f634f108f4299eb649d8f9c
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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