4-Aminonicotinaldehyde → 2-(2,6-dichloro-3-nitro-phenyl)-N-(3-formyl-pyridin-4-yl)-acetamide

HRID 270693

Reaction equation

HRID 270693 reaction equation
[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[CH2:12][C:13]([OH:15])=O.[NH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[CH:23]=[O:24]>S(Cl)(Cl)=O.ClCCl.CCOC(C)=O>[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[CH2:12][C:13]([NH:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[CH:23]=[O:24])=[O:15]

Participants

6

Reactant 2

HCID 27610334-AminonicotinaldehydeHCID 542654372,6-Dichloro-3-nitrophenylacetic acid

Product 1

HCID 598338592-(2,6-dichloro-3-nitro-phenyl)-N-(3-formyl-pyridin-4-yl)-acetamideYield 95.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of (2,6-dichloro-3-nitro-phenyl)-acetic acid (15.0 g, 60.0 mmol) in thionyl chloride (60 mL) is refluxed for one hour. The solvent is removed by concentration; dry toluene is added and concentrated to thoroughly remove thionyl chloride. To the solution of acid chloride in dry dichloromethane (200 mL) is added (drop-wise) a solution of 4-amino-pyridine-3-carbaldehyde (6.6 g, 54 mmol) in dichloromethane (50 mL) and DIEDA (10.7 mL, 60 mmol). The mixture is at room temperature for 2 hours. The reaction mixture is diluted with EtOAc (300 ml) and washed with saturated K2CO3 and brine. The organic layer is dried, filtered and concentrated to give crude product. Recrystallization with dichloromethane/hexane results in the titled compound as a solid (18.2 g, 95.2%).

Workup

  1. customThe solvent is removed by concentration
  2. additiondry toluene is added
  3. concentrationconcentrated to thoroughly remove thionyl chloride
  4. washwashed with saturated K2CO3 and brine
  5. customThe organic layer is dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude product
  9. customRecrystallization with dichloromethane/hexane

Sources & evidence

ORD record
ord-c0ea74fc44c74a67a44b70cbc2269a15
Source dataset
uspto-grants-2008_11
Patent number
US07449582B2

Linked notes

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