Dichloromethane → tert-butyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595961Notes

Reaction equation

HRID 595961 reaction equation
[NH2:1][C:2]1[C:3]([C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[C:16]([F:27])[CH:15]=2)=[N:4][C:5]([C:8]2[CH2:9][CH2:10][O:11][CH2:12][CH:13]=2)=[CH:6][N:7]=1.C(Cl)Cl.[H][H]>CO.[Pd]>[NH2:1][C:2]1[C:3]([C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])=[C:16]([F:27])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 118045381tert-butyl 4-(3-amino-6-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoateHCID 178418361HCID 178418361, compound

Product 1

HCID 118046148tert-butyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoateYield 29.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a suspension of tert-butyl 4-(3-amino-6-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate (15 g, 40.4 mmol) in MeOH (800 mL) was added DCM (100 mL) until the suspension turned to a homogeneous solution. After degassed by N2 stream for 15 min, Pd/C (10 g, 9.40 mmol) was added to the reaction mixture. To this mixture, hydrogen balloon was equipped after flushed with hydrogen gas three times. The reaction mixture was stirred for 6 h. After the reaction mixture was filtered through Celite® pad, the volatile materials were removed in vacuo. The residue was dissolved in MeOH (200 mL) by heating and cooling down to room temperature and standing overnight. The brown precipitate was filtered off, which afforded 4.5 g of tert-butyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate. The filtrate was concentrated and dissolved in EtOH (200 mL) by heating. The second brown precipitate was filtered off to afford 3.9 g of tert-butyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate (55.7% combined yield). LCMS (m/z): 374.7 (MH+), 0.90 min.

Workup

  1. customAfter degassed by N2 stream for 15 min
  2. customafter flushed with hydrogen gas three times
  3. filtrationAfter the reaction mixture was filtered through Celite® pad
  4. customthe volatile materials were removed in vacuo
  5. dissolutionThe residue was dissolved in MeOH (200 mL)
  6. temperatureby heating
  7. waitstanding overnight
  8. filtrationThe brown precipitate was filtered off

Sources & evidence

ORD record
ord-c19dce60eab94c3ca418d18933583576
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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