Sodium Carbonate → 1,1-dimethylethyl (1S,4S,6S)-4-({[5-(trifluoromethyl)-2-pyrazinyl]amino}methyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate

HRID 1094767Notes

Reaction equation

HRID 1094767 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:9][C@H:8]2[C@H:6]([CH2:7]2)[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Br[C:18]1[CH:23]=[N:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:25][C:24]([F:27])([F:26])[C:21]1[N:22]=[CH:23][C:18]([NH:1][CH2:2][C@@H:3]2[CH2:9][C@H:8]3[C@H:6]([CH2:7]3)[CH2:5][N:4]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 569655942-Bromo-5-(trifluoromethyl)pyrazineHCID 593960081,1-dimethylethyl (1S,4S,6S)-4-(aminomethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate

Product 1

HCID 593960051,1-dimethylethyl (1S,4S,6S)-4-({[5-(trifluoromethyl)-2-pyrazinyl]amino}methyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1,1-dimethylethyl (1S,4S,6S)-4-(aminomethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate D29 (400 mg) and 2-bromo-5-(trifluoromethyl)pyrazine (401 mg, 1.767 mmol) were dissolved in DMF (2 ml) then sodium carbonate (375 mg, 3.53 mmol) was added and the mixture was heated to 50° C. for 2 hours. DMF was concentrated under vacuum and the residue was taken up with DCM (3 ml) and washed with NaHCO3 saturated solution (4 ml). The organic phase was filtered through a phase separator tube, concentrated under vacuum and purified by silica gel chromatography (Biotage SP—column size 25 g SNAP using Cy:EtOAc=8:2 to 2:8 as eluent). It was recovered the title compound D30 (300 mg).

Workup

  1. concentrationDMF was concentrated under vacuum
  2. washwashed with NaHCO3 saturated solution (4 ml)
  3. filtrationThe organic phase was filtered through a phase separator tube
  4. concentrationconcentrated under vacuum
  5. custompurified by silica gel chromatography (Biotage SP—column size 25 g SNAP using Cy:EtOAc=8:2 to 2:8 as eluent)
  6. customIt was recovered the title compound D30 (300 mg)

Sources & evidence

ORD record
ord-10f6007a04c34a2b915a10161900ea72
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

Loading…