Cesium carbonate → (R)-4-((R)-1-(3-bromo-6-(1-tert-butyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209238Notes

Reaction equation

HRID 2209238 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:15]=3)[CH:8]=[C:7]([OH:20])[C:6]=12.CS(O[C@H:26]([C@@H:28]1[CH2:32][C:31](=[O:33])[N:30]([C@@H:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH3:35])[CH2:29]1)[CH3:27])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([C:16]([CH3:17])([CH3:19])[CH3:18])[CH:15]=3)[CH:8]=[C:7]([O:20][C@@H:26]([C@H:28]3[CH2:29][N:30]([C@@H:34]([C:36]4[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)[CH3:35])[C:31](=[O:33])[CH2:32]3)[CH3:27])[C:6]=12

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 117842947(S)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethyl methanesulfonateHCID 1178429823-bromo-6-(1-tert-butyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-ol

Product 1

HCID 117843456(R)-4-((R)-1-(3-bromo-6-(1-tert-butyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To an appropriate sized microwave vial, 3-bromo-6-(1-tert-butyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-ol (60 mg, 0.18 mmol), (S)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethyl methanesulfonate 1.30 (73 mg, 0.21 mmol), cesium carbonate (82 mg, 0.25 mmol) and DMF were added. The mixture was heated at 90° C. for 2 h. After cooling to room temperature, the mixture was poured into a saturated aqueous solution of NaHCO3 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford (R)-4-((R)-1-(3-bromo-6-(1-tert-butyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 6.30.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-b80332d9a7644c0281e16da292d19f7a
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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