Sulfoxonium, trimethyl-, iodide (1:1) → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutyl-cyclopropyl)thiazolo[5,4-b]pyridine

HRID 1177592Notes

Reaction equation

HRID 1177592 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:24]2[CH2:27][CH2:26][CH2:25]2)=[CH2:23])[N:16]=3)=[C:9]([F:28])[CH:8]=1.[I-].[CH3:30][S+](C)(C)=O.CC([O-])(C)C.[K+]>C1COCC1.CS(C)=O>[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]2([CH:24]4[CH2:27][CH2:26][CH2:25]4)[CH2:30][CH2:23]2)[N:16]=3)=[C:9]([F:28])[CH:8]=1

Participants

6

Reactant 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 671120572-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutylvinyl)-thiazolo[5,4-b]pyridine

Product 1

HCID 671117962-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutyl-cyclopropyl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutylvinyl)-thiazolo[5,4-b]pyridine (167.1 mg, 0.421 mmol) in THF (8.0 mL) was added a solution of trimethylsulfoxonium iodide (557 mg, 2.53 mmol) and potassium 2-methylpropan-2-olate (284 mg, 2.53 mmol) in DMSO (4.80 mL) under argon, and the resulting solution was stirred at 60° C. for 2.5 h. The reaction mixture was then cooled to 25° C., THF was removed in vacuo, and the residual mixture was diluted with DCM (100 mL). The resulting solution was sequentially washed with sat. aq. NH4Cl (50 mL) and brine (20 mL). The combined aqueous layers were extracted with DCM (2×50 mL), and the combined organic layers were then 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-cyclobutyl-cyclopropyl)thiazolo[5,4-b]pyridine as a white solid. MS (ESI) m/z: Calculated: 410.1; Observed: 411.1 (M++1).

Workup

  1. temperatureThe reaction mixture was then cooled to 25° C.
  2. customTHF was removed in vacuo
  3. additionthe residual mixture was diluted with DCM (100 mL)
  4. washThe resulting solution was sequentially washed with sat. aq. NH4Cl (50 mL) and brine (20 mL)
  5. extractionThe combined aqueous layers were extracted with DCM (2×50 mL)
  6. dry with materialthe combined organic layers were then dried 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-b8aa7d397efc4c81ae5a92a11cca3b42
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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