Pyridine → Tacedinaline

HRID 846811Notes

Reaction equation

HRID 846811 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11](=[O:22])[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:21])[CH3:20])=[CH:14][CH:13]=1)([O-])=O.C(Cl)(=O)C(Cl)=O.CN(C)C=O.C(NC1C=CC(C(O)=O)=CC=1)(=O)C.N1C=CC=CC=1.[N+](C1C=CC=CC=1N)([O-])=O.[OH-].[Na+]>C(OCC)(=O)C>[NH:18]([C:15]1[CH:14]=[CH:13][C:12]([C:11]([NH:10][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH2:1])=[O:22])=[CH:17][CH:16]=1)[C:19]([CH3:20])=[O:21]

Participants

9

Reactant 7

HCID 1049Pyridine2×HCID 6228DimethylformamideHCID 69462-NitroanilineHCID 14798Sodium HydroxideHCID 19266p-Acetamidobenzoic acidHCID 65578Oxalyl chlorideHCID 3360305HCID 3360305, compound

Product 1

HCID 2746Tacedinaline

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

The N-(2'-nitrophenyl)-4-acetylaminobenzamide used as starting material is prepared as follows: 41.3 g (0.33 mole) oxalyl chloride are added dropwise at 0°-5° C., with the exclusion of moisture, to a solution of 60.3 g (0.83 mole) dimethylformamide in 1.5 L dry ethyl acetate. After stirring for 30 minutes at this temperature, 44.8 g (0.25 mole) 4-acetamidobenzoic acid, together with 27.7 g (0.35 mole) pyridine, are added thereto and the ice bath is removed. After stirring for 3 hours at ambient temperature, the reaction mixture is mixed with a solution of 38 g (0.28 mole) o-nitroaniline and 27.7 g (0.35 mole) pyridine in 30 mL dry ethyl acetate. After stirring for 15 hours at ambient temperature, the reaction mixture is mixed with 500 mL 1N aqueous sodium hydroxide solution, the phases are separated and the aqueous phase is shaken out three times with 150 mL amounts of ethyl acetate. The combined organic phases are washed neutral with water, dried over anhydrous sodium sulfate, and concentrated to about one-third. The precipitate obtained is filtered off with suction and purified either by recrystallization or by column chromatography. Yield 15 g (20% of theory); m.p. 205.8° C.

Workup

  1. customis prepared
  2. additionare added
  3. customthe ice bath is removed
  4. stirringAfter stirring for 15 hours at ambient temperature
  5. customthe phases are separated
  6. stirringthe aqueous phase is shaken out three times with 150 mL amounts of ethyl acetate
  7. washThe combined organic phases are washed neutral with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated to about one-third
  10. customThe precipitate obtained
  11. filtrationis filtered off with suction
  12. custompurified either by recrystallization or by column chromatography

Sources & evidence

ORD record
ord-474b85cfc3ef471fb49614faa5354998
Source dataset
uspto-grants-1992_08
Patent number
US05137918

Reaction notes

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