Water → HCID 117843199, compound

HRID 2209215Notes

Reaction equation

HRID 2209215 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([OH:12])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[CH3:11])[CH:7]=1.CS(O[C@H:18]([C@@H:20]1[CH2:24][C:23](=[O:25])[N:22]([C@@H:26]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH3:27])[CH2:21]1)[CH3:19])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([O:12][C@@H:18]([C@H:20]2[CH2:21][N:22]([C@@H:26]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[CH3:27])[C:23](=[O:25])[CH2:24]2)[CH3:19])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[CH3:11])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 117842947(S)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethyl methanesulfonateHCID 178430920HCID 178430920, compound

Product 1

HCID 117843199HCID 117843199, compoundYield 32.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-3-methylpyrazolo[1,5-a]pyrazin-4-ol 5.52 (48 mg, 0.262 mmol), (S)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethyl methanesulfonate 1.30 (135 mg, 0.394 mmol), and cesium carbonate (136 mg, 0.417 mmol) in DMF (2 mL) was heated at 90° C. After 5 hours, reaction mixture was cooled to rt, poured into water, and extracted with ethyl acetate. Combined organics were washed with 50% brine, dried, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate/hexanes) to yield (R)-4-((R)-1-((6-chloro-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 5.53 (37 mg).

Workup

  1. customreaction mixture
  2. temperaturewas cooled to rt
  3. extractionextracted with ethyl acetate
  4. washCombined organics were washed with 50% brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e1b5527d20f146c29131df9e2aa85aaf
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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