Methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoate → Methyl 4-(3-amino-6-(4-aminocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596049Notes

Reaction equation

HRID 596049 reaction equation
[NH2:1][C:2]1[C:3]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:32])[CH:23]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([NH:14]CC3C=CC=CC=3)[CH2:10][CH2:9]2)=[CH:6][N:7]=1.[H][H]>[Pd].CO>[NH2:1][C:2]1[C:3]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:32])[CH:23]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]2)=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 118045264Methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoateHCID 178418361HCID 178418361, compound

Product 1

HCID 118045844Methyl 4-(3-amino-6-(4-aminocyclohexyl)pyrazin-2-yl)-2-fluorobenzoateYield 82.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (350 mg, 0.806 mmol) in a round bottom flask that was flushed with argon was added Pd—C 10% degaussa, wet (171 mg, 0.161 mmol). Then under argon with syringe, was added MeOH (5 mL) and last a hydrogen balloon. The flask was evacuated and refilled with hydrogen six times. The reaction was stirred at room temperature for 14 h. The reaction was purged with argon, then Pd—C 10% degaussa, wet (171 mg, 0.161 mmol) was carefully added. Then a hydrogen balloon was added, and the flask was evacuated and refilled with hydrogen six times. The reaction was stirred for additional 10 h to give a total of 24 h, followed by LCMS. The reaction was flushed with argon and 35 mL of DCM was added. The crude mixture was filtered through a Celite plug, and concentrated to constant mass to give 230 mg of desired product (which is 2:1 trans to cis ratio), used as is (83%). LCMS (m/z): 345.2 (MH+), 0.48 min and 0.51 min.

Workup

  1. customThe flask was evacuated
  2. additionrefilled with hydrogen six times
  3. customThe reaction was purged with argon
  4. additionwet (171 mg, 0.161 mmol) was carefully added
  5. additionThen a hydrogen balloon was added
  6. customthe flask was evacuated
  7. additionrefilled with hydrogen six times
  8. stirringThe reaction was stirred for additional 10 h
  9. customto give a total of 24 h
  10. customThe reaction was flushed with argon and 35 mL of DCM
  11. additionwas added
  12. filtrationThe crude mixture was filtered through a Celite plug
  13. concentrationconcentrated to constant mass

Sources & evidence

ORD record
ord-ef9f58a6e091469eaabe91e5864e2c40
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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