Water → HCID 86648997, compound

HRID 518067Notes

Reaction equation

HRID 518067 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[N:12]=[C:11]([N:13]([CH:15]2[CH2:18][CH2:17][CH2:16]2)[CH3:14])[CH:10]=[N:9][CH:8]=1.O.CN([CH:23]=[O:24])C>>[Cl:6][C:7]1[C:8]([CH:23]=[O:24])=[N:9][CH:10]=[C:11]([N:13]([CH:15]2[CH2:16][CH2:17][CH2:18]2)[CH3:14])[N:12]=1

Participants

5

Reactant 4

HCID 962WaterHCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 866489966-chloro-N-cyclobutyl-N-methylpyrazin-2-amine

Product 1

HCID 86648997HCID 86648997, compoundYield 66%

Procedure

Phosphoryl chloride (4.3 mL) was added dropwise to DMF (20 mL) at 0° C., and the mixture was stirred for 20 min. To the reaction mixture was added a solution of 6-chloro-N-cyclobutyl-N-methylpyrazin-2-amine (4.61 g) in DMF (5 mL), and the mixture was stirred at 50° C. for 15 hr. Water was added to the reaction mixture and the mixture was stirred for 2 hr and extracted with ethyl acetate. The extract was washed with water and saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient: 10-450% ethyl acetate/hexane) and recrystallized from hexane-diisopropyl ether to give the title compound (3.46 g, 66%).

Workup

  1. stirringthe mixture was stirred at 50° C. for 15 hr
  2. stirringthe mixture was stirred for 2 hr
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (solvent gradient: 10-450% ethyl acetate/hexane)
  8. customrecrystallized from hexane-diisopropyl ether

Sources & evidence

ORD record
ord-412fac9a6cc14b50992d7b5489b185fc
Source dataset
uspto-grants-2015_08
Patent number
US09115139B2

Reaction notes

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