trans-Crotonyl chloride → HCID 69795238, compound

HRID 497592Notes

Reaction equation

HRID 497592 reaction equation
[C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[CH3:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[C:11]2[NH2:17]>N1C=CC=CC=1>[CH3:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[C:11]2[NH:17][C:1](=[O:5])[CH:2]=[CH:3][CH3:4]

Participants

4

Reactant 2

HCID 643131trans-Crotonyl chlorideHCID 223196385-Methyl-1H-indazol-3-amine

Product 1

HCID 69795238HCID 69795238, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

0.33 cm3 of crotonyl chloride is added to 560 mg of 5-methyl-1H-indazole-3-amine, prepared as described in patent EP 909 720, in 30 cm3 of pyridine. The medium is allowed to return to about 19° C. over 12 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 2×25 cm3 of distilled water. The resulting solution 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 (50/50 by volume) and collecting 20 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.), 50 mg of N-(5-methyl-1H-indazol-3-yl)-2-butenamide (E form) are obtained in the form of a white solid melting at about 218° C.

Workup

  1. customprepared
  2. customThe reaction medium is evaporated under reduced pressure (2 kPa; 50° C.)
  3. washThe organic phase is washed with 2×25 cm3 of distilled water
  4. dry with materialThe resulting solution 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 (50/50 by volume)
  9. customcollecting 20 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.), 50 mg of N-(5-methyl-1H-indazol-3-yl)-2-butenamide (E form)

Sources & evidence

ORD record
ord-3821355c252f4241be2ac2722b8cb408
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

Loading…