trans-Crotonyl chloride → N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide

HRID 497593

Reaktionsgleichung

Reaktionsgleichung von HRID 497593
[C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[F:7][C:8]([F:20])([F:19])[C:9]1[CH:17]=[C:16]2[C:12]([C:13]([NH2:18])=[N:14][NH:15]2)=[CH:11][CH:10]=1>N1C=CC=CC=1>[F:20][C:8]([F:7])([F:19])[C:9]1[CH:17]=[C:16]2[C:12]([C:13]([NH:18][C:1](=[O:5])[CH:2]=[CH:3][CH3:4])=[N:14][NH:15]2)=[CH:11][CH:10]=1

Komponenten

4

Edukt 2

HCID 643131trans-Crotonyl chlorideHCID 8179093-Amino-6-(trifluoromethyl)-1H-indazole

Produkt 1

HCID 69795078N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Versuchsvorschrift

0.23 cm3 of crotonyl chloride is added to 500 mg of 6-trifluoro methyl-1H-indazole-3-amine, prepared as described in patent U.S. Pat. No. 3,133,081, in 10 cm3 of pyridine, cooled to about 10° C. The temperature is allowed to return to about 19° C. over 17 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 25 cm3 of tetrahydrofuran, 25 cm3 of ethyl acetate and 25 cm3 of distilled water. The organic phase is washed with 25 cm3 of distilled water. The combined organic phases are dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under reduced pressure (2 kPa; 50° C.). The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume) and collecting 30 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). The residue is taken up in 30 cm3 of diisopropyl ether and then filtered off on a sinter funnel. After drying (90 Pa; 45° C.), 41 mg of N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide (E form) are obtained in the form of a white solid melting at 208° C.

Aufarbeitung

  1. customprepared
  2. customThe reaction medium is evaporated under reduced pressure (2 kPa; 50° C.)
  3. washThe organic phase is washed with 25 cm3 of distilled water
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. filtrationfiltered through a sinter funnel
  6. customevaporated under reduced pressure (2 kPa; 50° C.)
  7. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  8. washon a column of silica gel (particle size 40-60 μm; diameter 2 cm), eluting with a cyclohexane/ethyl acetate mixture (70/30 by volume)
  9. customcollecting 30 cm3 fractions
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. filtrationfiltered off on a sinter funnel
  13. dry with materialAfter drying (90 Pa; 45° C.), 41 mg of N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide (E form)

Quellen und Nachweise

ORD-Eintrag
ord-5839b9758203420f918401840f7641d3
Quelldatensatz
uspto-grants-2005_09
Patentnummer
US06949579B2

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