Bay-H-1127 → N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide

HRID 497594

Reaktionsgleichung

Reaktionsgleichung von HRID 497594
[C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[F:7][C:8]([F:20])([F:19])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[NH2:18]>N1C=CC=CC=1>[F:20][C:8]([F:7])([F:19])[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[NH:18][C:1](=[O:5])[CH:2]=[CH:3][CH3:4]

Komponenten

4

Edukt 2

HCID 16736Bay-H-1127HCID 643131trans-Crotonyl chloride

Produkt 1

HCID 67042757N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
19 °C

Versuchsvorschrift

0.24 cm3 of crotonyl chloride is added to 500 mg of 5-(trifluoromethyl)-1H-indazole-3-amine, prepared according to patent U.S. Pat. No. 3,133,081, in 15 cm3 of pyridine. The reaction medium is stirred at about 19° C. for 12 hours and then evaporated under reduced pressure (2 kPa; 50° C.). 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 again with 25 cm3 of distilled water. The organic phase is 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 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (40/60 by volume) and collecting 25 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 45° C.), 63 mg of N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide (E form) are obtained in the form of an off-white solid melting at about 242° C.

Aufarbeitung

  1. customprepared
  2. customevaporated under reduced pressure (2 kPa; 50° C.)
  3. washThe organic phase is washed again with 25 cm3 of distilled water
  4. dry with materialThe organic phase is 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 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (40/60 by volume)
  9. customcollecting 25 cm3 fractions
  10. additionThe fractions containing the expected product
  11. customevaporated under reduced pressure (2 kPa; 50° C.)
  12. dry with materialAfter drying (90 Pa; 45° C.), 63 mg of N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butenamide (E form)

Quellen und Nachweise

ORD-Eintrag
ord-a3821eb69d0e47ffb4b695423e23b243
Quelldatensatz
uspto-grants-2005_09
Patentnummer
US06949579B2

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