1-Methylpiperazine → HCID 46180121, compound

HRID 1909002Notes

Reaction equation

HRID 1909002 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[C:6]=2[CH:18]=1.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.CC([O-])(C)C.[Na+]>CC(O)(C)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH3:19][N:20]1[CH2:25][CH2:24][N:23]([C:2]2[CH:3]=[CH:4][C:5]3[N:9]=[CH:8][N:7]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[C:6]=3[CH:18]=2)[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 531671-MethylpiperazineHCID 23676156Sodium t-butoxideHCID 66599757HCID 66599757, compound

Product 1

HCID 46180121HCID 46180121, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

(Buchwald coupling): In a microwave reaction vial a suspension of 6-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazole (500 mg, 1.53 mmol), 1-methyl-piperazine (0.203 mL, 1.83 mmol) Pd2(dba)3 (0) (14 mg, 0.015 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (36 mg, 0.076 mmol) and NaOtBu (206 mg, 2.14 mmol) in 2-methyl-propan-2-ol (1.5 mL) was degassed with nitrogen. The reaction was heated in a microwave reaction at 100° C. for 1 hour. The mixture was diluted with H2O, acidified by the addition of 2M aqueous HCl, stirred with EtOAc and then filtered. The EtOAc layer was then extracted with H2O (×3). The combined aqueous fractions were neutralized with saturated NaHCO3 solution and then extracted with CHCl3/iPrOH (2:1) (×3). The combined extracts were dried (MgSO4), filtered and concentrated in vacuo. The product was purified by SiO2 chromatography providing the title compound (387 mg).

Workup

  1. custom(Buchwald coupling): In a microwave reaction vial
  2. customwas degassed with nitrogen
  3. additionThe mixture was diluted with H2O
  4. additionacidified by the addition of 2M aqueous HCl
  5. filtrationfiltered
  6. extractionThe EtOAc layer was then extracted with H2O (×3)
  7. extractionextracted with CHCl3/iPrOH (2:1) (×3)
  8. dry with materialThe combined extracts were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-98bf3f09fa62475eb35cfc92814a89cc
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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