6-chloro-1H-indazol-3-amine → N-(6-chloro-1H-indazol-3-yl)-2-butenamide

HRID 497586

Reaction equation

HRID 497586 reaction equation
[C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH2:17])=[N:13][NH:14]2)=[CH:10][CH:9]=1>N1C=CC=CC=1>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH:17][C:1](=[O:5])[CH:2]=[CH:3][CH3:4])=[N:13][NH:14]2)=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 856286-chloro-1H-indazol-3-amineHCID 643131trans-Crotonyl chloride

Product 1

HCID 69796956N-(6-chloro-1H-indazol-3-yl)-2-butenamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
6 °C

Procedure

0.67 cm3 of distilled crotonyl chloride is added to 50 mg of 6-chloro-1H-indazole-3-amine dissolved in 5 cm3 of pyridine and cooled to about 6° C. The mixture is stirred for 10 minutes and the temperature is then allowed to rise to about 19° C. over 22 hours. The reaction medium is then concentrated to dryness under reduced pressure (2 kPa; 40° C.) and the residue is then taken up in 50 cm3 of tetrahydrofuran and 25 cm3 of ethyl acetate. The organic phase is washed with 2×50 cm3 of distilled water and then with 50 cm3 of saturated aqueous sodium chloride solution. The resulting solution is dried over magnesium sulphate, filtered through a sinter funnel and then evaporated under the conditions described previously. The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume) and collecting 20 cm3 fractions. The fractions containing the expected product are combined and then evaporated under the conditions already described. After drying (90 Pa; 45° C.), 100 mg of N-(6-chloro-1H-indazol-3-yl)-2-butenamide, E form, are obtained in the form of a white solid melting at 226° C.

Workup

  1. waitto rise to about 19° C. over 22 hours
  2. concentrationThe reaction medium is then concentrated to dryness under reduced pressure (2 kPa; 40° C.)
  3. washThe organic phase is washed with 2×50 cm3 of distilled water
  4. dry with materialThe resulting solution is dried over magnesium sulphate
  5. filtrationfiltered through a sinter funnel
  6. customevaporated under the conditions
  7. customThe residue obtained
  8. customis purified by chromatography under an argon pressure of 50 kPa
  9. washon a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  10. customcollecting 20 cm3 fractions
  11. additionThe fractions containing the expected product
  12. customevaporated under the conditions
  13. dry with materialAfter drying (90 Pa; 45° C.), 100 mg of N-(6-chloro-1H-indazol-3-yl)-2-butenamide, E form

Sources & evidence

ORD record
ord-e6900106e13040ef8d93cc8311c4932b
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Linked notes

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