Potassium hydride → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutylvinyl)-thiazolo[5,4-b]pyridine

HRID 1177591Notes

Reaction equation

HRID 1177591 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]([CH:29]2[CH2:32][CH2:31][CH2:30]2)(O)[CH2:23][Si](C)(C)C)[N:16]=3)=[C:9]([F:33])[CH:8]=1.[H-].[K+]>C1COCC1>[O:3]1[CH2:4][CH2:5][CH2:6][O:1][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]([CH:29]2[CH2:32][CH2:31][CH2:30]2)=[CH2:23])[N:16]=3)=[C:9]([F:33])[CH:8]=1

Participants

4

Reactant 2

HCID 82127Potassium hydrideHCID 671116841-(2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)-1-cyclobutyl-2-(trimethylsilyl)ethanol

Product 1

HCID 671120572-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutylvinyl)-thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

1-(2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)thiazolo[5,4-b]pyridin-5-yl)-1-cyclobutyl-2-(trimethylsilyl)ethanol (355.8 mg, 0.731 mmol) in THF (10.0 mL) was carefully added dropwise to potassium hydride (30 wt % in mineral oil; 293 mg, 2.193 mmol) (washed with hexanes (1×5 mL) to remove mineral oil) at 0° C. The resulting solution was heated at 65° C. for 3 h, and excess potassium hydride was then quenched by the sequential addition of water (4 mL) and sat. aq. NH4Cl (4 mL). THF was removed in vacuo, and the resulting mixture was diluted with EtOAc (100 mL) and sequentially washed with sat. aq. NH4Cl and brine. The combined aqueous layers were extracted with EtOAc, and all organic layers were then combined, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-30% EtOAc/hexanes) furnished 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutylvinyl)-thiazolo[5,4-b]pyridine as a white solid. MS (ESI) m/z: Calculated: 396.1; Observed: 397.1 (M++1).

Workup

  1. customexcess potassium hydride was then quenched by the sequential addition of water (4 mL) and sat. aq. NH4Cl (4 mL)
  2. customTHF was removed in vacuo
  3. additionthe resulting mixture was diluted with EtOAc (100 mL)
  4. washsequentially washed with sat. aq. NH4Cl and brine
  5. extractionThe combined aqueous layers were extracted with EtOAc
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-43f058a47378464d8ebe1c7928e1db0f
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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