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

HRID 1177598Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1177598
[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][C:26]([F:29])([F:28])[CH2:25]2)=[CH2:23])[N:16]=3)=[C:9]([F:30])[CH:8]=1.[I-].[CH3:32][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][C:26]([F:29])([F:28])[CH2:25]4)[CH2:32][CH2:23]2)[N:16]=3)=[C:9]([F:30])[CH:8]=1

Komponenten

6

Edukt 3

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 23665647Potassium tert-butoxideHCID 671119192-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)vinyl)thiazolo[5,4-b]pyridine

Produkt 1

HCID 671115762-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)vinyl)thiazolo[5,4-b]pyridine (299.1 mg, 0.692 mmol) in THF (13.33 mL) was added a solution of trimethylsulfoxonium iodide (913 mg, 4.15 mmol) and potassium 2-methylpropan-2-olate (466 mg, 4.15 mmol) in DMSO (8.0 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 (200 mL). The resulting solution was sequentially washed with sat. aq. NH4Cl and brine). The combined aqueous layers were extracted with DCM, and the combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-70% EtOAc/hexanes) furnished 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-(3,3-difluoro-cyclobutyl)cyclopropyl)thiazolo[5,4-b]pyridine as a light yellow solid. MS (ESI) m/z: Calculated: 446.1; Observed: 447.1 (M++1).

Aufarbeitung

  1. temperatureThe reaction mixture was then cooled to 25° C.
  2. customTHF was removed in vacuo
  3. additionthe residual mixture was diluted with DCM (200 mL)
  4. washThe resulting solution was sequentially washed with sat. aq. NH4Cl and brine)
  5. extractionThe combined aqueous layers were extracted with DCM
  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, 0-70% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5965e2e4166f428ab9208b120fc8e08c
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842685B2

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