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

HRID 604198Notes

Reaction equation

HRID 604198 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1.[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[C:42]([CH:44]([CH3:46])[CH3:45])[CH:41]=[CH:40][C:39]=2[O:47][CH3:48])=[C:34]([CH2:49]Cl)[CH:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[C:42]([CH:44]([CH3:46])[CH3:45])[CH:41]=[CH:40][C:39]=2[O:47][CH3:48])=[C:34]([CH2:49][N:7]([CH2:6][C:5]2[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=[C:3]([C:2]([F:1])([F:22])[F:23])[CH:4]=2)[C:8]2[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=2)[CH:33]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57551007(3,5-Bis-trifluoromethyl-benzyl)-(5-bromopyrimidin-2-yl)-amineHCID 670872924-Benzyloxy-2-chloromethyl-5'-isopropyl-2'-methoxy-biphenyl

Product 1

HCID 86626927(4-Benzyloxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amineYield 78.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (315 mg) and 4-benzyloxy-2-chloromethyl-5′-isopropyl-2′-methoxy-biphenyl (300 mg) are dissolved in N,N-dimethylformamide (5 ml) and thereto is added sodium hydride (60%) (40.9 mg) under ice-cooling, and the mixture is stirred at room temperature overnight. Thereto are added a saturated aqueous ammonium chloride solution and ethyl acetate, and the mixture is separated, and 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=1:0→97:3) to give (4-benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (458 mg). MS (m/z): 744/746 [M+H]+

Workup

  1. temperaturecooling
  2. customthe mixture is separated
  3. washthe organic layer is washed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→97:3)

Sources & evidence

ORD record
ord-69f82cc1e97f413287103983a7e90899
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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