Chloroform → HCID 67030555, compound

HRID 1465501Notes

Reaction equation

HRID 1465501 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[CH:19]=[C:20]([CH2:23][CH2:24][C:25]([O:27]C)=O)[S:21][CH:22]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].O.[NH2:30][NH2:31].C(Cl)(Cl)[Cl:33]>CO>[ClH:33].[ClH:33].[ClH:33].[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[CH:19]=[C:20]([CH2:23][CH2:24][C:25]([NH:30][NH2:31])=[O:27])[S:21][CH:22]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 24654Hydrazine hydrate (1:1)HCID 58181253HCID 58181253, compound

Product 1

HCID 67030555HCID 67030555, compoundYield 75.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
47.5 °C

Procedure

To a solution of methyl 3-(4-{2-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]ethyl}thiophen-2-yl)propanoate (360.0 mg, 0.897 mmol) in anhydrous methanol (14 ml) was added hydrazine monohydrate (449 mg, 8.97 mmol), and the mixture was stirred at 45 to 50° C. for 2 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in 10% methanol-dichloromethane mixture and filtered through aminopropylated silica gel. The filtrate was concentrated under reduced pressure, and the residue was purified by aminopropylated silica gel column chromatography (2% methanol-dichloromethane mixture) to give a colorless oil. This was dissolved in anhydrous chloroform (30 ml), and 1M hydrogen chloride diethyl ether solution (4.0 ml, 4.0 mmol) was added dropwise. After stirring for 15 min, the reaction mixture was concentrated under reduced pressure. Anhydrous chloroform (30 ml) was added to the residue, and the mixture was concentrated under reduced pressure. This operation was repeated 3 times to removed excess hydrogen chloride azeotropically. The residue was suspended in anhydrous chloroform (30 ml), filtered, washed with anhydrous chloroform, anhydrous diethyl ether and ethyl acetate, and dried under reduced pressure to give the title compound (347.5 mg, yield 75.8%) as a slightly yellow white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in 10% methanol-dichloromethane mixture
  3. filtrationfiltered through aminopropylated silica gel
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by aminopropylated silica gel column chromatography (2% methanol-dichloromethane mixture)
  6. customto give a colorless oil
  7. stirringAfter stirring for 15 min
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. additionAnhydrous chloroform (30 ml) was added to the residue
  10. concentrationthe mixture was concentrated under reduced pressure
  11. customto removed excess hydrogen chloride azeotropically
  12. filtrationfiltered
  13. washwashed with anhydrous chloroform, anhydrous diethyl ether and ethyl acetate
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-acde2097abd0415da3b455ecea585dca
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

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