Trifluoroacetic acid → HCID 58181270, compound

HRID 1465494Notes

Reaction equation

HRID 1465494 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH2:17][C:18]3[S:22][C:21]([C:23]([NH:25][NH:26]C(OC(C)(C)C)=O)=[O:24])=[CH:20][CH:19]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH2:17][C:18]3[S:22][C:21]([C:23]([NH:25][NH2:26])=[O:24])=[CH:20][CH:19]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 58181339HCID 58181339, compound

Product 1

HCID 58181270HCID 58181270, compoundYield 75.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 2-[(5-{2-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]ethyl}thiophen-2-yl)carbonyl]hydrazinecarboxylate (300.0 mg) in anhydrous dichloromethane (15 ml) was added trifluoroacetic acid (0.91 ml, 12.3 mmol) at 0° C. After stirring at room temperature for 1 hr, the mixture was cooled again to 0° C., and trifluoroacetic acid (0.91 ml, 12.3 mmol) was added. After stirring at room temperature for 12.5 hrs, the reaction mixture was concentrated under reduced pressure. Ethyl acetate (30 ml) was added to the residue, and the mixture was concentrated again under reduced pressure. This operation was repeated 3 times to remove trifluoroacetic acid azeotropically. The residue was purified by aminopropylated silica gel column chromatography (2-propanol:dichloromethane=1:9). The fraction containing the target product was concentrated to about 20 ml under reduced pressure, and hexane (50 ml) was added. This operation was repeated 3 times to crystallize the target product. Hexane (100 ml) was added to the mixture, and the precipitate was filtered, washed with a mixed solvent of diethyl ether-hexane (1:1), and dried under reduced pressure to give the title compound (173.2 mg, yield 75.7%) as a white solid.

Workup

  1. temperaturethe mixture was cooled again to 0° C.
  2. stirringAfter stirring at room temperature for 12.5 hrs
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. additionEthyl acetate (30 ml) was added to the residue
  5. concentrationthe mixture was concentrated again under reduced pressure
  6. customto remove trifluoroacetic acid azeotropically
  7. customThe residue was purified by aminopropylated silica gel column chromatography (2-propanol:dichloromethane=1:9)
  8. additionThe fraction containing the target product
  9. concentrationwas concentrated to about 20 ml under reduced pressure, and hexane (50 ml)
  10. additionwas added
  11. customto crystallize the target product
  12. additionHexane (100 ml) was added to the mixture
  13. filtrationthe precipitate was filtered
  14. washwashed with a mixed solvent of diethyl ether-hexane (1:1)
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-842a4f3c0d3d494e8213d27275872219
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

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