Water → Ethyl 4-(2'-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4'-trifluoromethyl-biphenyl-2-yloxy)-butyrate

HRID 604116Notes

Reaction equation

HRID 604116 reaction equation
[F:1][C:2]([F:46])([F:45])[C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=1[C:31]1[C:32]([OH:37])=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][N:9]=1.Br[CH2:48][CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C(OCC)(=O)C>[F:46][C:2]([F:1])([F:45])[C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([C:41]([F:43])([F:42])[F:44])[CH:40]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][C:22]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[O:37][CH2:48][CH2:49][CH2:50][C:51]([O:53][CH2:54][CH3:55])=[O:52])[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 866268652'-{[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4'-trifluoromethyl-biphenyl-2-ol

Product 1

HCID 86626866Ethyl 4-(2'-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4'-trifluoromethyl-biphenyl-2-yloxy)-butyrate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2′-{[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4′-trifluoromethyl-biphenyl-2-ol (150 mg) is dissolved in N,N-dimethylformamide (3 ml) and thereto are added ethyl 4-bromobutyrate (50 μl) and potassium carbonate (47 mg), and the mixture is stirred at room temperature for 2 hours and at 80° C. for 2 hours. The reaction solution is cooled to room temperature, and thereto are added water 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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→4:1) to give ethyl 4-(2′-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4′-trifluoromethyl-biphenyl-2-yloxy)-butyrate (163 mg). MS (m/z): 771 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→4:1)

Sources & evidence

ORD record
ord-6394db25275e405bbbaf4b1507279daf
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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