Acetic Acid → HCID 89690480, compound

HRID 1481886Notes

Reaction equation

HRID 1481886 reaction equation
C(O)C.C(O)(=O)C.[Cl:8][C:9]1[CH:26]=[C:25]([N:27]2[CH2:32][CH2:31][N:30]([C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[CH2:29][CH2:28]2)[C:24]([N+:41]([O-])=O)=[CH:23][C:10]=1[C:11]([NH:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][C:18]1=[O:22])=[O:12]>[Fe]>[NH2:41][C:24]1[C:25]([N:27]2[CH2:28][CH2:29][N:30]([C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[CH2:31][CH2:32]2)=[CH:26][C:9]([Cl:8])=[C:10]([CH:23]=1)[C:11]([NH:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][C:18]1=[O:22])=[O:12]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 89692898HCID 89692898, compound

Product 1

HCID 89690480HCID 89690480, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Procedure

In a 50 ml round bottom flask equipped with a magnetic stir bar and fitted with a septum and a nitrogen inlet, the iron powder (377 mg, 6.75 mmol) was suspended in clean, dry, reagent-grade ethanol (12 ml, 205.52 mmol) and allowed to stir at room temperature under nitrogen. To this was added the acetic acid (1.20 ml, 20.96 mmol) and the reaction was allowed to stir to ensure homogeneity. The 2-chloro-4-[4-(5-fluoro-2-methyl-phenyl)-piperazin-1-yl]-5-nitro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 16f (140.10 mg, 0.27 mmol) was added in one portion and the reaction was warmed to 75° C. and allowed to stir for 3 h. After 3 h, the reaction was cooled to room temperature and filtered through Celite, washing heavily with methanol. The collected organic solution was then concentrated under reduced pressure and the resultant red oil was taken up in 50 ml of ethyl acetate and was washed with 50 ml of saturated NaHCO3 (aq) solution. The product was then extracted from the aqueous using ethyl acetate (3×20 ml) and the organic phases were combined, washed with brine (1×50 ml) and dried over Na2SO4. The solution was then decanted, and the solvent was removed under reduced pressure. The product, 5-amino-2-chloro-4-[4-(5-fluoro-2-methyl-phenyl)-piperazin-1-yl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 16g (130 mg, 0.27 mmol), was isolated as a brown solid and carried forward without further purification. LCMS (m/e)=488 (M+H).

Workup

  1. customIn a 50 ml round bottom flask equipped with a magnetic stir bar
  2. customfitted with a septum and a nitrogen inlet
  3. customdry
  4. stirringto stir
  5. temperaturethe reaction was warmed to 75° C.
  6. stirringto stir for 3 h
  7. temperaturethe reaction was cooled to room temperature
  8. filtrationfiltered through Celite
  9. washwashing heavily with methanol
  10. concentrationThe collected organic solution was then concentrated under reduced pressure
  11. washwas washed with 50 ml of saturated NaHCO3 (aq) solution
  12. extractionThe product was then extracted from the
  13. washwashed with brine (1×50 ml)
  14. dry with materialdried over Na2SO4
  15. customThe solution was then decanted
  16. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-d42265e14f7e4a1897b91664dac7d9a5
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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