6-chloro-1H-indazol-3-amine → Ethyl (2E) 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate

HRID 497583Notes

Reaction equation

HRID 497583 reaction equation
[C:1]([O:8][CH2:9][CH3:10])(=[O:7])/[CH:2]=[CH:3]/[C:4]([O-:6])=O.[Cl:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]([NH2:21])=[N:17][NH:18]2)=[CH:14][CH:13]=1.Cl.CN(C)CCCN=C=NCC>ClCCl>[Cl:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]([NH:21][C:4](=[O:6])/[CH:3]=[CH:2]/[C:1]([O:8][CH2:9][CH3:10])=[O:7])=[N:17][NH:18]2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 856286-chloro-1H-indazol-3-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58782252-Butenedioic acid, monoethyl ester

Product 1

HCID 9994564Ethyl (2E) 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

865 mg of monoethyl fumarate are added to 1 g of 6-chloro-1H-indazole-3-amine in 50 cm3 of dichloromethane. 1.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are then introduced and the mixture is stirred for 30 minutes at about 20° C. The resulting mixture is washed with 50 cm3 of distilled water and then with 50 cm3 of saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate, filtered and then evaporated under reduced pressure (2 kPa; 40° C.). 2 g of a brick-coloured gummy mass are obtained, and are 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 (90/10 by volume) and collecting 40 cm3 fractions. The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. After drying (90 Pa; 45° C.), 900 mg of ethyl 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate, (E form), melting at 220° C., are obtained.

Workup

  1. washThe resulting mixture is washed with 50 cm3 of distilled water
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated under reduced pressure (2 kPa; 40° C.)
  5. custom2 g of a brick-coloured gummy mass are obtained
  6. customare purified by chromatography under an argon pressure of 50 kPa
  7. washon a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  8. customcollecting 40 cm3 fractions
  9. additionThe fractions containing the expected product
  10. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C
  11. dry with materialAfter drying (90 Pa; 45° C.), 900 mg of ethyl 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate, (E form), melting at 220° C.
  12. customare obtained

Sources & evidence

ORD record
ord-2ef5ea5d1f334a49874480b70d8de61b
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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