Piperazine → HCID 89825954, compound

HRID 1775370Notes

Reaction equation

HRID 1775370 reaction equation
Br[C:2]1[C:3]([CH3:9])=[N+:4]([O-:8])[CH:5]=[CH:6][CH:7]=1.CC(C)([O-])C.[Na+].[NH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C>O1CCOCC1.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]>[CH3:9][C:3]1[C:2]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:7][CH:6]=[CH:5][N+:4]=1[O-:8]

Participants

7

Reactant 4

HCID 4837PiperazineHCID 144029523-Bromo-2-methylpyridine N-oxideHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 89825954HCID 89825954, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

3-Bromo-2-methyl-pyridine 1-oxide (a total of 388 mg, 2.06 mmol), sodium tert-butoxide (a total of 392 mg, 4.08 mmol), piperazine (a total of 651 mg, 7.56 mmol) and RuPhos (a total of 58 mg, 0.12 mmol) were divided in three batches and dissolved in anhydrous dioxane (total volume of 15 ml), and purged with argon for 5 minutes. A total of Pd2(DBA)3 (60 mg, 0.064 mmol) was added and each batch was heated in a closed vial for 22 hours at 90° C. The combined reaction mixtures were filtered through kieselguhr and concentrated under reduced pressure to give a brown oil that was purified by column chromatography (silica, gradient from 0 to 10% of methanol containing 7N ammonia in DCM) to give 170 mg (0.88 mmol, yield 43%) MS (multi-mode) m/z=194.1 [M+1]+.

Workup

  1. custompurged with argon for 5 minutes
  2. customThe combined reaction mixtures
  3. filtrationwere filtered through kieselguhr
  4. concentrationconcentrated under reduced pressure
  5. customto give a brown oil that
  6. customwas purified by column chromatography (silica, gradient from 0 to 10% of methanol containing 7N ammonia in DCM)
  7. customto give 170 mg (0.88 mmol, yield 43%)

Sources & evidence

ORD record
ord-e7d5fa066dd843d3bb242d29785de595
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

Loading…