Tetrahydrofuran → 3-(4-cyanophenoxy)-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20558

Reaktionsgleichung

Reaktionsgleichung von HRID 20558
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:22])[CH2:19][O:20][CH3:21])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C1COCC1.F[C:39]1[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][CH:40]=1>CN(C=O)C>[C:43]([C:42]1[CH:45]=[CH:46][C:39]([O:1][C:2]2[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:22])[CH2:19][O:20][CH3:21])[CH:16]=2)[C:5]([NH:7][C:8]2[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=2)=[O:6])=[CH:40][CH:41]=1)#[N:44]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 145174-Fluorobenzonitrile2×HCID 2724254Sodium bis(trimethylsilyl)amide3×HCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Produkt 1

HCID 116543663-(4-cyanophenoxy)-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.164 mmol) in DMF (1 mL) was added a 1M solution of sodium hexamethyldisilazide in THF (0.164 mmol). The reaction was stirred at RT for 10 minutes before adding 4-fluorobenzonitrile (0.164 mmol) The reaction was stirred overnight at RT, then heated to 60° C. and stirred for a further 4 hours. The reaction was allowed to cool to RT, and treated with a further 0.2 equivalents of 4-fluorobenzonitrile and sodium hexamethyldisilazide, heated to 70° C. and stirred at this temperature for 3 hours. The reaction was cooled to RT, and treated with a further 0.2 equivalents of sodium hexamethyldisilazide, warmed to 70° C., and stirred at this temperature overnight. The solvent was removed in vacuo and the residual oil partitioned between ethyl acetate and water. The water layer was separated and re-extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to a residue which was chromatographed on silica, using 0-1% methanol in DCM as the eluent, to give the desired product (60% yield).

Aufarbeitung

  1. stirringwas stirred overnight at RT
  2. temperatureheated to 60° C.
  3. stirringstirred for a further 4 hours
  4. temperatureto cool to RT
  5. temperatureheated to 70° C.
  6. stirringstirred at this temperature for 3 hours
  7. temperatureThe reaction was cooled to RT
  8. temperaturewarmed to 70° C.
  9. stirringstirred at this temperature overnight
  10. customThe solvent was removed in vacuo
  11. customthe residual oil partitioned between ethyl acetate and water
  12. customThe water layer was separated
  13. extractionre-extracted with ethyl acetate
  14. washThe combined organic layers were washed with brine
  15. dry with materialdried (MgSO4)
  16. filtrationfiltered
  17. customevaporated to a residue which
  18. customwas chromatographed on silica

Quellen und Nachweise

ORD-Eintrag
ord-7d8dd7fe79354dd1b89a5fd35ae7e023
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745475B2

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