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

HRID 1427120
Notes
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Reaction equation

HRID 1427120 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.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[C:29]([CH3:30])=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][C:20]=1[CH3:31].N1C=CC=CC=1>C1COCC1.C(Cl)Cl.CN(C)C1C=CN=CC=1.CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:18][C:19]2[C:20]([CH3:31])=[CH:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:28][C:29]=2[CH3:30])=[O:10])[C:5]([CH3:11])=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 1049PyridineHCID 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 4

HCID 6228DimethylformamideCatalyst
HCID 142844-(Dimethylamino)pyridineCatalyst
HCID 6344DichloromethaneSolvent
HCID 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 μmoles) 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 μmoles) 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-f663261d49954143a37789ad86d8cedf
Source dataset
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08933098B2

Reaction notes

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