1-Methylpiperazine → 1-(5-Bromopyridin-3-yl)-4-methylpiperazine

HRID 1878618Notes

Reaction equation

HRID 1878618 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[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]>[Br:8][C:6]1[CH:7]=[C:2]([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 693693,5-DibromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxide

Product 1

HCID 534853141-(5-Bromopyridin-3-yl)-4-methylpiperazine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 3,5-dibromopyridine (Sigma-Aldrich, St. Louis, USA) (1 eq, 8.4 mmol, 2.0 g) and 1-methylpiperazine (Sigma-Aldrich, St. Louis, USA) (1 eq, 8.4 mmol, 0.94 ml) in toluene (20 ml), Pd2(dba)3 (0.02 eq, 0.167 mmol, 153 mg), Xantphos (0.06 eq, 0.50 mmol, 290 mg), and NaOtBu (1.5 eq, 12.5 mmol, 1.2 g) are added. The resulting mixture is heated using microwave radiation at 120° C. for 15 min. The solvents are evaporated and aqueous HCl solution (1 M) is added. The aqueous layer is washed with DCM, adjusted to pH 10, and extracted with DCM. The organic layer is dried, filtered, and concentrated to give the title compound, [M+H]+=257.

Workup

  1. temperatureThe resulting mixture is heated
  2. customat 120° C.
  3. customfor 15 min
  4. customThe solvents are evaporated
  5. additionaqueous HCl solution (1 M) is added
  6. washThe aqueous layer is washed with DCM
  7. extractionextracted with DCM
  8. customThe organic layer is dried
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-d0234e594aaa4d9988e06d176707d95b
Source dataset
uspto-grants-2012_11
Patent number
US08314112B2

Reaction notes

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