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

HRID 239912Notes

Reaction equation

HRID 239912 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.[NH2:12][C:13]1[C:23]([CH3:24])=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][C:14]=1[CH3:25].C(N(CC)C(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:12][C:13]2[C:14]([CH3:25])=[CH:15][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][C:23]=2[CH3:24])=[O:10])[C:5]([CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 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 57.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-chloro-3-methyl-pyridine-2-carboxylic acid (0.78 g, 4.55 mmol) in CH2Cl2 (15 mL) at room temperature are added ethyl 4-amino-3,5-dimethyl-benzoate (0.878 g, 4.55 mmol) and N,N-diisopropylethylamine (1.98 ml, 11.36 mmol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 3.25 ml, 5.46 mmol) is added via syringe. After 48 hours, the solvent is removed under reduced pressure and the residue is diluted with water and extracted with ethyl acetate. The organic layers are combined and dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using a gradient of 0-40% ethyl acetate in hexanes. After purification, the solid is triturated with 30% ethyl acetate in hexanes and filtered to give the title compound as a white powder (0.907 g, 57.5%). Mass spectrum (m/z): 347.2 (M+1).

Workup

  1. waitAfter 48 hours
  2. customthe solvent is removed under reduced pressure
  3. additionthe residue is diluted with water
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by flash chromatography (silica gel)
  9. customAfter purification
  10. customthe solid is triturated with 30% ethyl acetate in hexanes
  11. filtrationfiltered

Sources & evidence

ORD record
ord-9fa3c5cd6f834b8fb1880df9095e743b
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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