Carbonate Ion → 1-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-indazol-4-amine

HRID 551426

Reaktionsgleichung

Reaktionsgleichung von HRID 551426
CC1C=CC(S(O[CH2:12][C:13]2([C:16]([F:19])([F:18])[F:17])[CH2:15][O:14]2)(=O)=O)=CC=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([NH2:36])[C:30]=3[CH:29]=[N:28]2)=[CH:23][CH:22]=1.[Bi](Cl)(Cl)Cl.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-]>ClCCl.C(Cl)(Cl)Cl.O1CCCC1.[Bi](Cl)(Cl)Cl.CN(C=O)C>[F:20][C:21]1[CH:22]=[CH:23][C:24]([N:27]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([NH:36][CH2:12][C:13]4([C:16]([F:17])([F:18])[F:19])[CH2:15][O:14]4)[C:30]=3[CH:29]=[N:28]2)=[CH:25][CH:26]=1

Komponenten

11

Edukt 5

HCID 19660Carbonate IonHCID 24591Bismuth trichlorideHCID 81531DiisopropylethylamineHCID 24809749(2-(Trifluoromethyl)oxiran-2-yl)methyl 4-methylbenzenesulfonateHCID 249380581-(4-Fluorophenyl)-1H-indazol-4-amine

Produkt 1

HCID 249380561-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-indazol-4-amineAusbeute 59,1 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24591Bismuth trichlorideKatalysatorHCID 6212ChloroformLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

[2-(trifluoromethyl)-2-oxiranyl]methyl 4-methylbenzenesulfonate (6.14 g, 20.75 mmol) and 1-(4-fluorophenyl)-1H-indazol-4-amine (4.73 g, 20.75 mmol) in dry dichloromethane (5 ml) were stirred for 5 min. Bismuth chloride (654 mg, 2.07 mmol) was added and the mixture stirred at room temperature over the weekend. More bismuth chloride (0.33 g, 1.05 mmol) was then added and the mixture stirred overnight. The reaction was finally stirred overnight under nitrogen (to reduce the volume of DMF). There was no further progress on leaving for a further night. The reaction mixture was then diluted with chloroform (200 ml) and tetrahydrofuran (50 ml). N,N-Diisopropylethylamine (0.54 ml, 3.11 mmol) was added followed by polymer supported carbonate resin (Fluka, ca. 3.5 mmoles carbonate/g resin, 11.91 g) and the mixture stirred overnight. More THF (30 ml) was then added followed after 2 hours by some 4 A molecular sieves. After a further 3 hours LCMS indicated the reaction to be complete and the mixture was filtered. The filtrate was washed with water, the aqueous phase was back-extracted with dichloromethane and the combined organic phases were dried and evaporated to give crude product which was purified by silica gel chromatography using the Flashmaster II (2×100 g cartridges) eluting with a 0 to 50% dichloromethane:ethyl acetate gradient to give the title compound (4.31 g).

Aufarbeitung

  1. stirringthe mixture stirred overnight
  2. customon leaving for a further night
  3. stirringthe mixture stirred overnight
  4. waitfollowed after 2 hours by some 4
  5. waitAfter a further 3 hours LCMS indicated
  6. customthe reaction
  7. filtrationthe mixture was filtered
  8. washThe filtrate was washed with water
  9. extractionthe aqueous phase was back-extracted with dichloromethane
  10. customthe combined organic phases were dried
  11. customevaporated
  12. customto give crude product which
  13. customwas purified by silica gel chromatography
  14. washeluting with a 0 to 50% dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-b42ab2c801bc40188d392c1cf60a3bcb
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07947727B2

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