Triphenylphosphine → (3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-[5-(2-methylsulfanyl-ethoxy)-pyrimidin-2-yl]-amine

HRID 604139Notes

Reaction equation

HRID 604139 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:8]1[N:13]=[CH:12][C:11]([OH:14])=[CH:10][N:9]=1.[CH3:46][S:47][CH2:48][CH2:49]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.[Cl-].[Na+].O>[F:43][C:40]([F:41])([F:42])[C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:44])[F:45])[CH:39]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:49][CH2:48][S:47][CH3:46])=[CH:12][N:13]=1

Participants

8

Reactant 5

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 789252-(Methylthio)ethanol2×HCID 66777355Diethylazodicarboxylate tolueneHCID 866268722-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol

Product 1

HCID 86626886(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-[5-(2-methylsulfanyl-ethoxy)-pyrimidin-2-yl]-amine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

2-[(3,5-Bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol (300 mg) is dissolved in tetrahydrofuran (2 mL), and thereto are added 2-(methylthio)ethanol (162 μl) and triphenylphosphine (488 mg), and thereto is added dropwise a 40% diethyl azodicarboxylate/toluene solution (424 μl) under water-cooling, and the mixture is stirred at 50° C. overnight. Further thereto are added 2-(methylthio)ethanol (243 μl) and triphenylphosphine (244 mg), and thereto is added dropwise diisopropyl azodicarboxylate (361 μl) under water-cooling, and the mixture is stirred at 60° C. for 2 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 silica gel column chromatography (hexane:ethyl acetate=99:1→9:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-[5-(2-methylsulfanyl-ethoxy)-pyrimidin-2-yl]-amine (300 mg). MS (m/z): 718 [M+H]+

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture is stirred at 60° C. for 2 hours
  4. extractionthe mixture is extracted with ethyl acetate
  5. washThe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=99:1→9:1)

Sources & evidence

ORD record
ord-082fc8172518437cac479441b5ab6e28
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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