5-(2-methyl-3,6-dihydro-2H-pyran-4-yl)pyrazin-2-amine → 5-((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)pyrazin-2-amine

HRID 595841Notes

Reaction equation

HRID 595841 reaction equation
[CH3:1][CH:2]1[CH2:7][C:6]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[CH:5][CH2:4][O:3]1>CO.[Pd]>[CH3:1][C@@H:2]1[CH2:7][C@H:6]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:5][CH2:4][O:3]1.[CH3:1][C@H:2]1[CH2:7][C@@H:6]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:5][CH2:4][O:3]1

Participants

5

Reactant 1

HCID 1180453955-(2-methyl-3,6-dihydro-2H-pyran-4-yl)pyrazin-2-amine

Product 2

HCID 1180455405-((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)pyrazin-2-amineHCID 1180462845-((2S,4S)-2-methyltetrahydro-2H-pyran-4-yl)pyrazin-2-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 5-(2-methyl-3,6-dihydro-2H-pyran-4-yl)pyrazin-2-amine (250 mg, 1.307 mmol) in MeOH (13.100 mL) was added Pd/C (278 mg, 0.261 mmol). The solution was degassed by N2 stream for 10 min. After flushed by H2 gas, hydrogen balloon was equipped. The reaction mixture was stirred for 25 h. After filtered through Celite, the volatile material was removed to give the crude product, which was purified with flash chromatography eluting with 0-10% of MeOH in DCM to provide 180 mg of diastereomers. Then chiral separation (ChiralPak 5mic AD column, 4.6×100 (mm), 5 mL/min, EtOH+0.1% DEA=15%) provided 40 mg of 5-((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)pyrazin-2-amine (Rt=1.32 min; LCMS (m/z): 194.2 (MH+), 0.44 min) in 22% yield and 30 mg of desired 5-((2S,4S)-2-methyltetrahydro-2H-pyran-4-yl)pyrazin-2-amine (Rt=1.83 min; LCMS (m/z): 194.2 (MH+), 0.44 min) in 16% yield.

Workup

  1. customThe solution was degassed by N2 stream for 10 min
  2. customAfter flushed by H2 gas, hydrogen balloon
  3. customwas equipped
  4. filtrationAfter filtered through Celite
  5. customthe volatile material was removed
  6. customto give the crude product, which
  7. customwas purified with flash chromatography
  8. washeluting with 0-10% of MeOH in DCM
  9. customto provide 180 mg of diastereomers
  10. customThen chiral separation (ChiralPak 5mic AD column, 4.6×100 (mm), 5 mL/min, EtOH+0.1% DEA=15%)

Sources & evidence

ORD record
ord-38c145efa9d948d6bd47063dc932bead
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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