trans-Crotonyl chloride → HCID 10246368, compound

HRID 497587Notes

Reaction equation

HRID 497587 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]([NH2:24])=[N:13][N:14]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:10][CH:9]=1>ClCCl.C(N(CC)CC)C>[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH:24][C:1](=[O:5])[CH2:2][CH:3]=[CH2:4])=[N:13][N:14]2[C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])=[CH:10][CH:9]=1

Participants

5

Reactant 2

HCID 643131trans-Crotonyl chlorideHCID 10423126HCID 10423126, compound

Product 1

HCID 10246368HCID 10246368, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
19 °C

Procedure

0.45 cm3 of predistilled crotonyl chloride is added to 1 g of 6-chloro-1-[(1,1-dimethylethoxy)carbonyl]-1H-indazole-3-amine described previously, in 40 cm3 of dichloromethane and 1.05 cm3 of triethylamine. The mixture is stirred at about 19° C. for 16 hours. The medium is then concentrated under reduced pressure (20 kPa; 40° C.). The residue is taken up in 100 cm3 of ethyl acetate and 50 cm3 of distilled water. The organic phase is then washed 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 already described previously. The residue is purified by chromatography under an argon pressure of 50 kPa, on silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume) and collecting 15 cm3 fractions. The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.). After drying (90 Pa; 45° C.), 120 mg of N-(6-chloro-1-[(1,1-dimethylethoxy)carbonyl]-1H-indazol-3-yl)-3-butenamide are obtained in the form of a yellow solid.

Workup

  1. concentrationThe medium is then concentrated under reduced pressure (20 kPa; 40° C.)
  2. washThe organic phase is then washed with 50 cm3 of saturated aqueous sodium chloride solution
  3. dry with materialThe resulting solution is dried over magnesium sulphate
  4. filtrationfiltered through a sinter funnel
  5. customevaporated under the conditions
  6. customThe residue is purified by chromatography under an argon pressure of 50 kPa
  7. washon silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  8. customcollecting 15 cm3 fractions
  9. additionThe fractions containing the expected product
  10. customevaporated under reduced pressure (2 kPa; 40° C.)
  11. dry with materialAfter drying (90 Pa; 45° C.), 120 mg of N-(6-chloro-1-[(1,1-dimethylethoxy)carbonyl]-1H-indazol-3-yl)-3-butenamide
  12. customare obtained in the form of a yellow solid

Sources & evidence

ORD record
ord-0a8e5bd8c96d494d97d4b9aa75263147
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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