Hydrazine → HCID 59812882, compound

HRID 2114589Notes

Reaction equation

HRID 2114589 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:12]2[C:13]([NH:26][CH2:27][CH:28]([OH:30])[CH3:29])=[N:14][C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])=[CH:16][C:11]=2[NH:10][N:9]=1.C(N(CC)C(C)C)(C)C.NN>O1CCOCC1.CCO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:12]2[C:13]([NH:26][CH2:27][C@@H:28]([OH:30])[CH3:29])=[N:14][C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])=[CH:16][C:11]=2[NH:10][N:9]=1

Participants

6

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 68878045HCID 68878045, compound

Product 1

HCID 59812882HCID 59812882, compoundYield 35.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[4,3-c]pyridin-4-ylamino]-propan-2-ol (690 mg, 1.6 mmol) was taken up in a mixture of 15 mL dioxane and 2 mL EtOH. N,N-diisopropylethylamine (0.3 mL) and anhydrous hydrazine (0.15 mL) were added, and the reaction mixture was slowly heated to 90° C. with stirring. The reaction mixture was stirred for six hours at 90° C., then was cooled to room temperature and quenched by addition of water and partitioned with ethyl acetate, followed by back extraction of the aqueous phase with additional ethyl acetate. The combined organic phases were washed with saturated brine and water, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by preparative scale TLC (3.5% MeOH in methylene chloride), then recrystallized from methylene chloride/hexanes to give 246 mg of (S)-1-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[4,3-c]pyridin-4-ylamino]-propan-2-ol. Mass spec., M+1=432. Mp=171.2-172° C.

Workup

  1. stirringThe reaction mixture was stirred for six hours at 90° C.
  2. temperaturewas cooled to room temperature
  3. customquenched by addition of water
  4. custompartitioned with ethyl acetate
  5. extractionfollowed by back extraction of the aqueous phase with additional ethyl acetate
  6. washThe combined organic phases were washed with saturated brine and water
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative scale TLC (3.5% MeOH in methylene chloride)
  11. customrecrystallized from methylene chloride/hexanes

Sources & evidence

ORD record
ord-2351477e1d6b4d17840ec67502abe216
Source dataset
uspto-grants-2008_10
Patent number
US07435731B2

Reaction notes

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