Tetrahydrofuran → (R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one

HRID 2209198Notes

Reaction equation

HRID 2209198 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.[OH:16][C@H:17]([C@H:19]1[CH2:23][NH:22][C:21](=[O:24])[CH2:20]1)[CH3:18].Cl[C:26]1[C:27]2[N:28]([N:42]=[CH:43][CH:44]=2)[CH:29]=[C:30]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34]([O:40][CH3:41])[CH:33]=2)[N:31]=1>CN(C=O)C>[CH3:41][O:40][C:34]1[CH:33]=[C:32]([C:30]2[N:31]=[C:26]([O:16][C@@H:17]([C@H:19]3[CH2:23][NH:22][C:21](=[O:24])[CH2:20]3)[CH3:18])[C:27]3[N:28]([N:42]=[CH:43][CH:44]=3)[CH:29]=2)[CH:37]=[CH:36][C:35]=1[O:38][CH3:39]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66713239(R)-4-((S)-1-hydroxyethyl)pyrrolidin-2-oneHCID 1178433844-Chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazine

Product 1

HCID 117842949(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1M sodium bis(trimethylsilyl) amide in THF (0.18 mL, 0.18 mmol) was added to a solution of (R)-4-((R)-1-hydroxyethyl)pyrrolidin-2-one 1.18 (22.9 mg, 0.18 mmol) in DMF (1 mL) at room temperature, forming a white precipitate. After 8 minutes, a solution of 4-chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazine 5.03 (34 mg, 0.12 mmol) in DMF (1.1 mL) was added under argon. Dark brown solution stirred at room temperature overnight. Mixture was quenched by addition of water, brine and ethyl acetate and layers were separated. Aqueous was extracted with ethyl acetate and combined organic layers were washed with 50% brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Resulting residue was purified by silica gel column chromatography (0-10% methanol in dichloromethane) to yield (R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one 5.04.

Workup

  1. customforming a white precipitate
  2. customMixture was quenched by addition of water, brine and ethyl acetate and layers
  3. customwere separated
  4. extractionAqueous was extracted with ethyl acetate
  5. washwere washed with 50% brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customResulting residue was purified by silica gel column chromatography (0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-ed98a13adaa74609add288d599d1f8eb
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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