Triacetoxyperiodinane → 1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]-3-[3-(1H-imidazol-2-yl)pyrazolo[3,4-b]pyridin-1-yl]pyrrolidin-2-one

HRID 522322Notes

Reaction equation

HRID 522322 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[C:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH:15]2[CH2:19][CH2:18][N:17]([C:20]3[CH:21]=[N:22][N:23]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C:24]=3[CH:25]([CH3:27])[CH3:26])[C:16]2=[O:35])[N:7]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CS(C)=O>[F:34][C:31]1[CH:32]=[CH:33][C:28]([N:23]2[C:24]([CH:25]([CH3:27])[CH3:26])=[C:20]([N:17]3[CH2:18][CH2:19][CH:15]([N:8]4[C:9]5=[N:10][CH:11]=[CH:12][CH:13]=[C:14]5[C:6]([C:2]5[NH:3][CH:4]=[CH:5][N:1]=5)=[N:7]4)[C:16]3=[O:35])[CH:21]=[N:22]2)=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 867230363-[3-(4,5-dihydro-1H-imidazol-2-yl)pyrazolo[3,4-b]pyridin-1-yl]-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one

Product 1

HCID 1362158841-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]-3-[3-(1H-imidazol-2-yl)pyrazolo[3,4-b]pyridin-1-yl]pyrrolidin-2-oneYield 82.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-[3-(4,5-dihydro-1H-imidazol-2-yl)pyrazolo[3,4-b]pyridin-1-yl]-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one (0.085 g, 0.18 mmol) and Dess-Martin periodinane (0.153 g, 0.36 mmol) in DMSO (2.5 mL) was stirred at 80° C. for 1 hr. It was then cooled to room temperature, quenched with sat. aq. NaHCO3 (50 mL), and extracted with EtOAc (50 mL). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo and purified by flash chromatography (SiO2, 0˜7% MeOH/EtOAc gradient elution) to give the title compound (0.070 g, 82%). 1H NMR (400 MHz, CDCl3) δ 10.42 (s, 1H, br), 8.74 (dd, J=8.4, 1.6 Hz, 1H), 8.54 (dd, J=4.8, 1.6 Hz, 1H), 7.64 (s, 1H), 7.40 (dd, J=6.8, 4.6 Hz, 2H), 7.23 (m, 1H), 7.18 (dd, J=8.6 Hz, 2H), 6.94 (s, 1H, br), 5.94 (dd, J=9.2, 9.2 Hz, 1H), 3.94 (m, 3H), 3.07 (heptet, J=6.8, 1H), 2.75-2.95 (m, 2H), 1.33 (d, J=7.6 Hz, 3H), 1.28 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C25H23FN8O [M+H]+471.2. found 471.2.

Workup

  1. temperatureIt was then cooled to room temperature
  2. customquenched with sat. aq. NaHCO3 (50 mL)
  3. extractionextracted with EtOAc (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (SiO2, 0˜7% MeOH/EtOAc gradient elution)

Sources & evidence

ORD record
ord-b94c8743ff3c45699035575a9a8361e2
Source dataset
uspto-grants-2016_05
Patent number
US09328116B2

Reaction notes

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