Piperazine → HCID 86711932, compound

HRID 1475240Notes

Reaction equation

HRID 1475240 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[N:9][C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)=[N:7]1.[NH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(O[Na])(C)(C)C.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C>C1(C)C=CC=CC=1.O.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]>[CH3:11][C:10]1[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([N:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)[CH:30]=[CH:29][CH:28]=2)[N:7]=[C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)[N:9]=1

Participants

8

Reactant 4

HCID 4837PiperazineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86711906HCID 86711906, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 86711932HCID 86711932, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-(1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (Example 11, Step 1; 500 mg, 1.04 mmol) in toluene (10 mL) were added piperazine (86 mg, 1.04 mmol), t-BuONa (290 mg, 3 mmol), Ruphos (46 mg, 0.1 mmol) and Pd2(dba)3 (90 mg, 0.1 mmol). The reaction mixture was then heated in a sealed vial at 110° C. under inert atmosphere for 12 h. The resulting mixture was cooled, diluted with H2O (30 mL) and extracted with EtOAc (2×20 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE:EA=3:1 to 1:1) to give the title compound as a white solid; MS (ES+) C23H22F3N7O2 requires: 485. found: 486 [M+H]+; 1H NMR (500 MHz, DMSO-d6) δ 8.78 (br s, 1H), 8.22 (d, J=9 Hz, 2H), 7.61 (d, J=9 Hz, 2H), 7.27 (m, 1H), 6.97 (m, 2H), 6.76 (d, J=7.5 Hz, 1H), 5.50 (s, 2H), 3.32 (m, 2H), 3.23 (m, 4H), 2.58 (s, 3H), 2.50 (m, 2H).

Workup

  1. temperatureThe resulting mixture was cooled
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (PE:EA=3:1 to 1:1)

Sources & evidence

ORD record
ord-7dda08603a2d4293ab085dc0ea5c8b54
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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