Pyridine → Ethyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoate

HRID 239967Notes

Reaction equation

HRID 239967 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[C:5]([CH3:11])=[CH:4][CH:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[C:34]([CH3:35])=[CH:33][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:26][C:25]=1[CH3:36].N1C=CC=CC=1>C1COCC1.C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:23][C:24]2[C:25]([CH3:36])=[CH:26][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:33][C:34]=2[CH3:35])=[O:10])[C:5]([CH3:11])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 201013Benzoic acid, 4-amino-3,5-dimethyl-, ethyl esterHCID 469414706-Chloro-3-methylpyridine-2-carboxylic acid

Product 1

HCID 86707305Ethyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoateYield 84.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-chloro-3-methyl-pyridine-2-carboxylic acid (465 mg, 2.71 mmol) in THF (5 ml), CH2Cl2 (5 ml) and DMF (0.01 ml, 129.33 moles) is added dropwise oxalyl chloride (0.3 ml, 3.46 mmoles) at 0° C. and reaction mixture is slowly allowed to warm to ambient temperature. After 2 hours, the solvent is removed under reduced pressure and the residue. To the residue CH2Cl2 (20 ml) is added and reaction mixture is cooled to 0° C., then ethyl 4-amino-3,5-dimethyl-benzoate (520 mg, 2.69 mmol) is added followed by N,N-dimethylpyridin-4-amine (15 mg, 122.78 moles) and Pyridine (0.66 ml, 8.16 mmoles). The cooling bath is removed and the clear yellow solution is allowed to warm to ambient temperature. After 1 hour, the solvent is removed and the reaction mixture is diluted with ethyl acetate and washed with 0.5N HCl, saturated solution of sodium bicarbonate, and brine. The organic layers are combined and dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by flash chromatography (silica gel) using 0-50% ethyl acetate in hexanes to give the title compound as a solid (790 mg, 84%). Mass spectrum (m/z): 347.2 (M+1).

Workup

  1. customreaction mixture
  2. customthe solvent is removed under reduced pressure
  3. additionTo the residue CH2Cl2 (20 ml) is added
  4. customreaction mixture
  5. temperatureis cooled to 0° C.
  6. customThe cooling bath is removed
  7. temperatureto warm to ambient temperature
  8. waitAfter 1 hour
  9. customthe solvent is removed
  10. additionthe reaction mixture is diluted with ethyl acetate
  11. washwashed with 0.5N HCl, saturated solution of sodium bicarbonate, and brine
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-68484cdc4aba4d0391974d5cb40bc41f
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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