Trifluoroacetic acid → HCID 178489382, compound

HRID 886612Notes

Reaction equation

HRID 886612 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]([OH:27])[CH2:25][OH:26])[CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[N:11](COCC[Si](C)(C)C)[N:10]=1.FC(F)(F)C(O)=O>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]([OH:27])[CH2:25][OH:26])[CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[NH:11][N:10]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59825012HCID 59825012, compound

Product 1

HCID 178489382HCID 178489382, compoundYield 12.5%

Procedure

1-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-ethane-1,2-diol (114 mg, 0.232 mmol) was treated with 2 mL trifluoroacetic acid for 5 h. The solution was concentrated and co-evaporated with tetrahydrofuran (2×), then dissolved in ethyl acetate, washed with saturated sodium bicarbonate (1×), brine (1×), and dried over sodium sulfate. The material was purified by preparative HPLC and shown to contain hydroxymethyl attached to the product (28 mg). Therefore, the material was treated with 100 mg PS-trisamine (Argonaut Technologies, Inc.) in tetrahydrofuran at 50° C. for 15 h., filtered and the resin was washed with tetrahydrofuran/methanol and concentrated to afford 1-{3-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-ethane-1,2-diol (10.5 mg, 12.5%). 1H-NMR (500 MHz, dimethylsulfoxide-d6) δ 3.45 (t, J=6.0 Hz, 2H), 3.79 (s, 3H), 4.56 (q, J=5 Hz, 1H), 4.67 (t, J=6 Hz, 1H), 5.23 (d, J=4 Hz, 1H), 7.03 (t, J=7.0 Hz, 1H), 7.15 (d, J=8 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.40 (t, J=8.5 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.58 (dd, J=7.5 Hz, J=2.0 Hz, 1H), 7.62 (s, 1H), 8.24 (d, J=2.5 Hz, 1H), 8.75 (d, J=2.5 Hz, 1H).

Workup

  1. concentrationThe solution was concentrated and co-evaporated with tetrahydrofuran (2×)
  2. dissolutiondissolved in ethyl acetate
  3. washwashed with saturated sodium bicarbonate (1×), brine (1×)
  4. dry with materialdried over sodium sulfate
  5. customThe material was purified by preparative HPLC
  6. additionTherefore, the material was treated with 100 mg PS-trisamine (Argonaut Technologies, Inc.) in tetrahydrofuran at 50° C. for 15 h.
  7. filtrationfiltered
  8. washthe resin was washed with tetrahydrofuran/methanol
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d48b6d7574744427a770bf6c24e11196
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

Loading…