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

HRID 239970Notes

Reaction equation

HRID 239970 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](C(O)=O)[C:5]([CH3:11])=[CH:4][CH:3]=1.[CH3:12][N:13]([CH:15]=[O:16])C.[C:17](Cl)(=O)C(Cl)=O.N[C:24]1(C)[CH:33]=[C:32](C)[CH:31]=[C:26]([C:27]([O:29][CH3:30])=[O:28])[CH2:25]1.N1C=CC=CC=1>C1COCC1.C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:15]([NH:13][C:12]2[C:25]([CH3:17])=[C:26]([CH:31]=[CH:32][C:33]=2[CH3:24])[C:27]([O:29][CH3:30])=[O:28])=[O:16])[C:5]([CH3:11])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 469414706-Chloro-3-methylpyridine-2-carboxylic acidHCID 86707353Methyl 3-amino-3,5-dimethylbenzoate

Product 1

HCID 86707343Methyl 3-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-2,4-dimethyl-benzoateYield 73.6%

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 the reaction mixture is slowly allowed to warm to ambient temperature. After 2 hours, the solvent is removed under reduced pressure. To the residue CH2Cl2 (20 ml) is added and reaction mixture is cooled to 0° C., then methyl 3-amino-3,5-dimethylbenzoate (490 mg, 2.73 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 solution is allowed to warm to ambient temperature. After 1.5 hours, 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 to give the title compound as a light yellow solid (664 mg, 73%). Mass spectrum (m/z): 333.2 (M+1).

Workup

  1. customthe solvent is removed under reduced pressure
  2. additionTo the residue CH2Cl2 (20 ml) is added
  3. customreaction mixture
  4. temperatureis cooled to 0° C.
  5. customThe cooling bath is removed
  6. temperatureto warm to ambient temperature
  7. waitAfter 1.5 hours
  8. customthe solvent is removed
  9. additionthe reaction mixture is diluted with ethyl acetate
  10. washwashed with 0.5N HCl, saturated solution of sodium bicarbonate, and brine
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eb45665575d249bab71135b370cf9852
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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