Morpholine → HCID 58966532, compound

HRID 390748Notes

Reaction equation

HRID 390748 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:6][N:7]([C:29]1[CH:34]=[N:33][C:32](Br)=[CH:31][N:30]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[CH:19]([N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH:20]([CH3:22])[CH3:21].[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[CH:19]([N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH:20]([CH3:22])[CH3:21])[C:29]1[CH:34]=[N:33][C:32]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[CH:31][N:30]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 58966545HCID 58966545, compound

Product 1

HCID 58966532HCID 58966532, compoundYield 100%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a solution of (3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrazin-2-yl)-[2-(2-methyl-1-morpholin-4-yl-propyl)-5-trifluoromethyl-benzyl]-amine (28 mg, 0.040 mmol) in toluene (0.5 mL) was added morpholine (0.01, 0.048 mmol), BINAP (5 mg, 0.004 mmol), sodium t-butoxide (6 mg, 0.056 mmol), and tris(dibenzylideneacetone)dipalladium (4 mg, 0.002 mmol). The mixture was heated at 80° C. overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered over a pad of silica gel. Mother liquor is concentrated. The residue was purified by flash chromatography (silica gel) (eluting with 10-50% ethyl acetate in hexanes) to afford the title compound as a yellow orange gum (20 mg. 0.04 mmol).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered over a pad of silica gel
  3. concentrationMother liquor is concentrated
  4. customThe residue was purified by flash chromatography (silica gel) (eluting with 10-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-34056e197f9b4e238c21555438b41267
Source dataset
uspto-grants-2013_02
Patent number
US08383660B2

Reaction notes

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