racemic cis-1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol → Racemic cis-1-(6-(5-(2,6-difluorophenyl)-1H-indazol-3-yl)-2-pyrazinyl)-3,4-piperidinediol 1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol

HRID 1529389Notes

Reaction equation

HRID 1529389 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C@H:33]([OH:36])[C@H:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1>Cl.CC(O)C>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C@H:33]([OH:36])[C@H:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1.[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][CH:33]([OH:36])[CH:32]([OH:37])[CH2:31]2)[CH:27]=[N:26][CH:25]=1

Participants

4

Reactant 1

HCID 67959584racemic cis-1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol

Product 1

HCID 88532872Racemic cis-1-(6-(5-(2,6-difluorophenyl)-1H-indazol-3-yl)-2-pyrazinyl)-3,4-piperidinediol 1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diolYield 29%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

A slurry of racemic cis-1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol (0.100 g, 0.197 mmol) in 3 mL 5-6 N HCl in IPA (acros organics) was sealed and the slurry was heated to 70° C. After 1.5 h, the reaction was cooled and concentrated in vacuo. This material was dissolved in DMSO and purified by shimadzu RPHPLC, 15-70% ACN/H2O with 0.1% TFA; product-containing fractions were concentrated in vacuo. The material was partitioned between sat'd aq NaHCO3 and DCM, and the aq. layer was extracted 3×10% MeOH/DCM. The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give the title compound (0.024 g, 29% yield) as an off-white solid: MS (ESI, pos. ion) m/z: 424 (M+1).

Workup

  1. temperaturethe reaction was cooled
  2. concentrationconcentrated in vacuo
  3. dissolutionThis material was dissolved in DMSO
  4. custompurified
  5. concentrationproduct-containing fractions were concentrated in vacuo
  6. customThe material was partitioned between sat'd aq NaHCO3 and DCM
  7. extractionthe aq. layer was extracted 3×10% MeOH/DCM
  8. dry with materialThe combined organics were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cff816d5e5d04f8d8bba0dc44c93f36d
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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