Morpholine → (4-Benzyloxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

HRID 604199Notes

Reaction equation

HRID 604199 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:16]=2[O:24][CH3:25])=[C:11]([CH2:26][N:27]([CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:28]2[N:33]=[CH:32][C:31](Br)=[CH:30][N:29]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH:77]1[CH2:82][CH2:81][O:80][CH2:79][CH2:78]1>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]>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:16]=2[O:24][CH3:25])=[C:11]([CH2:26][N:27]([CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:28]2[N:33]=[CH:32][C:31]([N:77]3[CH2:82][CH2:81][O:80][CH2:79][CH2:78]3)=[CH:30][N:29]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86626927(4-Benzyloxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine

Product 1

HCID 86626928(4-Benzyloxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amineYield 88%

Reagents, catalysts & solvents 3

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

Procedure

(4-Benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (433 mg) is dissolved in toluene (5 ml) and thereto are added tris(dibenzylideneacetone)dipalladium (107 mg), sodium tert-butoxide (168 mg), 2-(di-tert-butylphosphino)biphenyl (69.4 mg) and morpholine (152 mg) and the mixture is stirred under nitrogen atmosphere at room temperature overnight. To the reaction solution 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 silica gel column chromatography (hexane:ethyl acetate=9:1→2:1) to give (4-benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (384 mg). MS (m/z): 751 [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 silica gel column chromatography (hexane:ethyl acetate=9:1→2:1)

Sources & evidence

ORD record
ord-c6d387298f2e403e91ad9fb2b9daf409
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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