HCID 117842884, compound → HCID 90467374, compound

HRID 2209200Notes

Reaction equation

HRID 2209200 reaction equation
COC1C=CC([C@H]([N:11]2[CH2:15][C@H:14]([C@H:16]([O:18][C:19]3[C:20]4[N:21]([N:37]=[CH:38][C:39]=4[CH3:40])[CH:22]=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([N:31]5[CH2:36][CH2:35][O:34][CH2:33][CH2:32]5)=[CH:27][CH:26]=4)[N:24]=3)[CH3:17])[CH2:13][C:12]2=[O:41])C)=CC=1>C(O)(C(F)(F)F)=O.C(OCC)(=O)C>[CH3:40][C:39]1[CH:38]=[N:37][N:21]2[CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH2:32][CH2:33][O:34][CH2:35][CH2:36]4)=[CH:27][CH:26]=3)[N:24]=[C:19]([O:18][C@@H:16]([C@H:14]3[CH2:15][NH:11][C:12](=[O:41])[CH2:13]3)[CH3:17])[C:20]=12

Participants

4

Reactant 1

HCID 117842884HCID 117842884, compound

Product 1

HCID 90467374HCID 90467374, compound

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

(R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-4R)-1-(3-methyl-6-(4-morpholinophenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one 5.12 (34 mg, 0.061 mmol) was taken up in TFA (1.5 mL) and mixture was heated at 60° C. overnight. After cooling to room temperature, mixture was concentrated under reduced pressure and resulting film was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate. Layers were separated and aqueous was extracted with ethyl acetate. Combined organics were washed with 1:1 brine/saturated aqueous sodium bicarbonate, dried (Na2SO4), filtered, and concentrated under reduced pressure. Resulting residue was purified by prep HPLC and then silica gel column chromatography (0-15% methanol in dichloromethane) to yield (R)-4-((R)-1-(3-methyl-6-(4-morpholinophenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one 5.13.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationmixture was concentrated under reduced pressure
  3. customresulting film
  4. washwashed with saturated aqueous sodium bicarbonate
  5. customLayers were separated
  6. extractionaqueous was extracted with ethyl acetate
  7. washCombined organics were washed with 1:1 brine/saturated aqueous sodium bicarbonate
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customResulting residue was purified by prep HPLC

Sources & evidence

ORD record
ord-9aa58454d9294123b1bd91e0f749ee43
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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