Benzophenone imine → 1-[4-(2-Amino-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

HRID 1355461Notes

Reaction equation

HRID 1355461 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[C:6]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:18])[CH3:17])[CH2:12][CH2:11]2)[CH:5]=[CH:4][N:3]=1.CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=[NH:84])(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.CCOCC.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]>[NH2:84][C:2]1[C:7]([CH3:8])=[C:6]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:18])[CH3:17])[CH2:12][CH2:11]2)[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 185068191-[4-(2-Chloro-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanoneHCID 23676156Sodium t-butoxide

Product 1

HCID 185068801-[4-(2-Amino-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

1-[4-(2-Chloro-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone (free base, 0.040 g, 0.15 mmol), NaOtBu (0.020 g, 0.21 mmol), BINAP (0.014 g, 0.020 mmol), and Pd2dba3 (0.0068 g, 0.0103 mmol) were stirred in 1 mL anhydrous toluene under N2. Benzophenone imine (0.030 mL, 0.18 mmol) was added and the reaction was heated to 80° C. After 3 h the reaction was cooled to RT, diluted with Et2O, filtered through celite, and concentrated in vacuo. To the residue was added 1:1 THF/1M HCl. The mixture was stirred for 2 h, then washed 2× w/EtOAc. The aqueous phase was adjusted to pH 10 with Na2CO3 (solid). The solution was extracted 3× with DCM/nBuOH (95:5), and the combined organic extracts were dried over Na2SO4, filtered, concentrated. The residue was purified by flash column chromatography (95:5-90:10 DCM/MeOH) to afford the pure titled compound. 1H NMR (CDCl3) δ7.89 (d, 1H, J=5.1 Hz), 6.65 (d, 1H, J=5.1 Hz), 4.45 (bs, 2H), 3.61 (t, 2H, J=4.9 Hz), 3.43 (m, 4H), 2.41 (t, 4H, J=5.2 Hz), 2.12 (s, 3H), 2.08 (s, 3H).

Workup

  1. temperatureAfter 3 h the reaction was cooled to RT
  2. filtrationfiltered through celite
  3. concentrationconcentrated in vacuo
  4. additionTo the residue was added 1:1 THF/1M HCl
  5. washwashed 2× w/EtOAc
  6. extractionThe solution was extracted 3× with DCM/nBuOH (95:5)
  7. dry with materialthe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography (95:5-90:10 DCM/MeOH)

Sources & evidence

ORD record
ord-445665e5f81e4fca83fa6f747fb4d934
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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