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

HRID 522329Notes

Reaction equation

HRID 522329 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:16]3[CH2:20][CH2:19][N:18]([C:21]4[CH:22]=[N:23][N:24]([C:29]5[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=5)[C:25]=4[CH:26]([CH3:28])[CH3:27])[C:17]3=[O:36])[N:9]=[C:10]([C:11]3[NH:12][CH2:13][CH2:14][N:15]=3)[C:3]=12.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CS(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:16]3[CH2:20][CH2:19][N:18]([C:21]4[CH:22]=[N:23][N:24]([C:29]5[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=5)[C:25]=4[CH:26]([CH3:27])[CH3:28])[C:17]3=[O:36])[N:9]=[C:10]([C:11]3[NH:12][CH:13]=[CH:14][N:15]=3)[C:3]=12

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 867230423-[4-amino-3-(4,5-dihydro-1H-imidazol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one

Product 1

HCID 1362158833-[4-amino-3-(1H-imidazol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-oneYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-[4-amino-3-(4,5-dihydro-1H-imidazol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]pyrrolidin-2-one (0.057 g, 0.12 mmol) and Dess-Martin periodinane (0.100 g, 0.23 mmol) in DMSO (3 mL) was stirred at 80° C. for 45 min. The mixture 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 reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to yield the title compound (0.035 g, TFA salt, 48%). 1H NMR (TFA salt) (400 MHz, CDCl3) δ 11.96 (s, 1H), 11.12 (s, 1H), 8.17 (s, 1H), 7.65 (s, 1H), 7.40 (dd, J=8.8, 4.4 Hz, 2H), 7.20 (dd, J=8.6, 8.6 Hz, 1H), 7.05 (s, 2H, br), 5.74 (dd, J=9.2, 9.2 Hz, 1H) 3.94 (dd, J=8.4, 4.4 Hz, 2H), 3.05 (m, 1H), 3.07 (septet, J=7.0 Hz, 1H), 2.87 (m, 2H), 1.31 (d, J=6.8 Hz, 3H), 1.27 (d, J=6.8 Hz, 3H); MS: (ES) m/z calculated for C24H23FN10O (free form) [M+H]+ 487.2. found 487.2.

Workup

  1. temperatureThe mixture 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 reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-1b9e1fd1532649acaae543a9d1a613fb
Source dataset
uspto-grants-2016_05
Patent number
US09328116B2

Reaction notes

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