Morpholine → HCID 25118344, compound

HRID 2400571Notes

Reaction equation

HRID 2400571 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)[N:14]=3)[O:10][N:9]=2)=[CH:4][CH:3]=1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)(C)C)=CC(C(C)(C)C)=CC=2C(C)(C)C)CCCCC1>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.O.C(O)(C)(C)C.CN(C=O)C>[CH3:18][C:16]1[N:15]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:14]=[C:13]([C:11]2[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[CH:3][CH:4]=3)[N:12]=2)[CH:17]=1

Participants

10

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 25118340HCID 25118340, compoundHCID 68514635HCID 68514635, compound

Product 1

HCID 25118344HCID 25118344, compoundYield 20.2%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(4-iodophenyl)-5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazole (Example 13, 200 mg, 0.44 mmol), morpholine (76 μl, 0.88 mmol), potassium carbonate (121 mg, 0.88 mmol), tris(dibenzylideneacetone)dipalladium (13 mg, 0.014 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-tert-butyl-1,1′-biphenyl (21 mg 0.044 mmol), DMF (1 ml) and tert-butanol (4 ml) was stirred at 80° C. for 15 h. The reaction mixture was cooled and water (100 mL) and ethyl acetate (100 mL) was added. The layers were separated and the organic layer was washed with water and brine and then dried with magnesium sulfate. The solvent was evaporated and the residue was purified, first using preparative HPLC, then via flash chromatography (silica, cyclohexane/ethyl acetate, 10:1→2:1) to afford the title compound as a white solid (37 mg, 20%): 1H NMR (400 MHz, CDCl3) 8.11 (d, 2H), 7.13 (d, 2H), 7.07 (d, 2H), 6.97 (d, 2H), 6.78 (s, 1H), 5.41 (s, 2H), 3.88 (m, 4H), 3.28 (m, 4H), 2.33 (s, 3H), 2.25 (s, 3H); ES-MS m/z 416 (MH)+, HPLC RT (Method D) 2.95 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe layers were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was purified

Sources & evidence

ORD record
ord-00105ead04d745ea95282efe829f4d95
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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