Morpholine → HCID 86626809, compound

HRID 604053Notes

Reaction equation

HRID 604053 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=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[N:26]([CH2:37][CH3:38])[C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:8]1[N:13]=[CH:12][C:11](Br)=[CH:10][N:9]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[NH:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]1.C(=O)(O)[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>[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=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[N:26]([CH2:37][CH3:38])[C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:8]1[N:13]=[CH:12][C:11]([N:75]2[CH2:80][CH2:79][O:78][CH2:77][CH2:76]2)=[CH:10][N:9]=1

Participants

9

Reactant 5

HCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 27342152-(Di-tert-butylphosphino)biphenyl2×HCID 23676156Sodium t-butoxide2×HCID 86626808Benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethyl-carbamate

Product 1

HCID 86626809HCID 86626809, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethyl-carbamate (1.28 g) is dissolved in toluene (15 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (159 mg), 2-(di-tert-butylphosphino)biphenyl (208 mg), sodium tert-butoxide (250 mg) and morpholine (230 μl) and the mixture is stirred under nitrogen atmosphere at room temperature overnight. To the reaction solution are added tris(dibenzylideneacetone)dipalladium (159 mg), 2-(di-tert-butylphosphino)biphenyl (208 mg) and sodium tert-butoxide (250 mg) and the mixture is stirred for 3 hours and a half. 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 benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethyl-carbamate (724 mg). MS (m/z): 742 [M+H]+

Workup

  1. stirringthe mixture is stirred for 3 hours
  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-dc1689f6b90d4bb39d7a6d2699b56fc3
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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