Water → (3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine

HRID 604120Notes

Reaction equation

HRID 604120 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29].[Br:39][C:40]1[CH:41]=[N:42][C:43](Cl)=[N:44][CH:45]=1.C(N(CC)C(C)C)(C)C.O>C1(C)C=CC=CC=1>[F:1][C:2]([F:37])([F:38])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=1)[CH2:6][N:7]([C:43]1[N:44]=[CH:45][C:40]([Br:39])=[CH:41][N:42]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:26])[CH3:27])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 59343883[3,5-Bis(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine

Product 1

HCID 86626868(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amineYield 67.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (3.0 g) is dissolved in toluene (20 ml) and thereto are added 5-bromo-2-chloropyrimidine (1.6 g) and N,N-diisopropylethylamine (1.4 ml) and the mixture is heated under reflux overnight. The reaction solution is allowed to cool to room temperature, and thereto is added water 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=40:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (2.6 g). MS (m/z): 708/706 [M+H]+

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux overnight
  3. extractionthe mixture is extracted 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=40:1)

Sources & evidence

ORD record
ord-570707c388a04ae6a6720fb4d068968f
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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