Ethyl 4-piperidinecarboxylate → 1-(2-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(ethoxycarbonyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yl)-ethyl piperidine-4-carboxylate

HRID 604046Notes

Reaction equation

HRID 604046 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=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[NH:26][C:27](=[O:31])[O:28][CH2:29][CH3:30])[C:8]1[N:13]=[CH:12][C:11](Br)=[CH:10][N:9]=1.[C:41](P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)[CH3:42].[CH3:62][C:63](C)([O-])C.[Na+].[NH:68]1[CH2:73][CH2:72][CH:71](C(OCC)=O)[CH2:70][CH2:69]1.[C:79](=[O:82])([OH:81])[O-].[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[NH:68]1[CH2:69][CH2:70][CH:71]([C:79]([O:81][CH:41]([C:11]2[CH:10]=[N:9][C:8]([N:7]([CH2:6][C:5]3[CH:4]=[C:3]([C:2]([F:39])([F:1])[F:40])[CH:34]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:32]=3)[CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=3[N:26]([C:27]([O:28][CH2:29][CH3:30])=[O:31])[CH2:62][CH3:63])=[N:13][CH:12]=2)[CH3:42])=[O:82])[CH2:72][CH2:73]1

Participants

9

Reactant 5

HCID 70770Ethyl 4-piperidinecarboxylateHCID 516892Sodium BicarbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86626802Ethyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-carbamate

Product 1

HCID 872631561-(2-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(ethoxycarbonyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yl)-ethyl piperidine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-carbamate (412 mg) is dissolved in toluene (5 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (112 mg), 2-(di-tert-butylphosphino)biphenyl (146 mg), sodium tert-butoxide (176 mg) and ethyl piperidine-4-carboxylate (140 μl), and the mixture is stirred under nitrogen atmosphere at room temperature overnight. To the reaction solution are added a saturated aqueous sodium bicarbonate 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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→4:1) to give 1-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(ethoxycarbonyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yl)-ethyl piperidine-4-carboxylate (72 mg). MS (m/z): 750 [M+H]+

Workup

  1. customthe mixture is separated
  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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→4:1)

Sources & evidence

ORD record
ord-658ad3b5b0b147299ba192d960d0dc1b
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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