HCID 59278428, compound → HCID 59278105, compound

HRID 1361280Notes

Reaction equation

HRID 1361280 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([C@@H:10]([NH:13][C:14]([C:16]2[C:17]3[CH:24]=[N:23][N:22]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[C:18]=3[CH:19]=[N:20][CH:21]=2)=[O:15])[CH2:11][CH3:12])[CH:7]=[CH:6][N:5]=1)(=[O:3])[CH3:2].[CH3:32][Li]>C1COCC1.C(OCC)C>[OH:3][C:1]([C:4]1[CH:9]=[C:8]([C@@H:10]([NH:13][C:14]([C:16]2[C:17]3[CH:24]=[N:23][N:22]([C:25]4[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=4)[C:18]=3[CH:19]=[N:20][CH:21]=2)=[O:15])[CH2:11][CH3:12])[CH:7]=[CH:6][N:5]=1)([CH3:32])[CH3:2]

Participants

5

Reactant 2

HCID 59278428HCID 59278428, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 59278105HCID 59278105, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a chilled (−78° solution of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [(S)-1-(2-acetyl-pyridin-4-yl)-propyl]-amide (32 mg, 0.08 mmol) in anhydrous THF (2 mL) was added a solution of 1.6 N methyl lithium (0.29 mL, 0.46 mmol) in diethyl ether. The reaction mixture was slowly warmed to room temperature. After 18 hours, the mixture was cooled to −78° C., quenched with saturated aqueous ammonium chloride and extracted with EtOAc (4×60 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 μM 30×150 mm column) using a gradient of 15-65% acetonitrile in water with 0.1% TFA. Fractions from the chromatography were concentrated, made basic by saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The solid was triturated with EtOAc-hexanes to afford the title.

Workup

  1. temperaturethe mixture was cooled to −78° C.
  2. customquenched with saturated aqueous ammonium chloride
  3. extractionextracted with EtOAc (4×60 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 μM 30×150 mm column)
  8. concentrationFractions from the chromatography were concentrated
  9. extractionextracted with EtOAc
  10. washThe organic layer was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe solid was triturated with EtOAc-hexanes
  15. customto afford the title

Sources & evidence

ORD record
ord-0dbdd60c0ecc41a3af620b8b228ac973
Source dataset
uspto-grants-2011_02
Patent number
US07879873B2

Reaction notes

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