Acetic Acid → HCID 89692824, compound

HRID 1481872Notes

Reaction equation

HRID 1481872 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]([CH3:39])[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]([CH3:39])[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 89692823HCID 89692823, compound

Product 1

HCID 89692824HCID 89692824, compoundYield 80.5%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Conditions

Temperature
75 °C

Procedure

In a 250 ml round bottom flask equipped with a magnetic stir bar and fitted with a septum with a nitrogen inlet, the iron powder (578.30 mg, 10.36 mmol) was suspended in clean, dry, reagent-grade ethanol (50.00 ml, 856.34 mmol) and was stirred vigorously at room temperature under nitrogen as the acetic acid (5.00 ml, 87.34 mmol) was added. The 2-chloro-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-5-nitro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 12c (212.90 mg, 0.41 mmol) was added in one portion and the reaction was warmed to 75° C. The reaction was allowed to stir for 4 h. After 4 h, the reaction was cooled to room temperature and filtered through Celite, eluting with methanol. The solvent was then removed under reduced pressure and the ruby red oil was taken up in 100 ml of ethyl acetate. 100 ml of saturated NaHCO3 was added to the solution. The layers were separated and the aqueous layer was extracted twice with 75 ml of ethyl acetate. The organic phases were combined and washed with brine (1×100 ml) and dried over Na2SO4. The product solution was decanted and the solvent was removed under reduced pressure. The crude product, 5-amino-2-chloro-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 12d (158.70 mg, 0.33 mmol), was isolated as a brown solid and was carried on without further purification. LCMS (m/e)=485 (M+H).

Workup

  1. customIn a 250 ml round bottom flask equipped with a magnetic stir bar
  2. customfitted with a septum with a nitrogen inlet
  3. customdry
  4. additionwas added
  5. waitAfter 4 h
  6. temperaturethe reaction was cooled to room temperature
  7. filtrationfiltered through Celite
  8. washeluting with methanol
  9. customThe solvent was then removed under reduced pressure
  10. addition100 ml of saturated NaHCO3 was added to the solution
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted twice with 75 ml of ethyl acetate
  13. washwashed with brine (1×100 ml)
  14. dry with materialdried over Na2SO4
  15. customThe product solution was decanted
  16. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f6f10fcbc26e481abf203834c84a35f4
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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