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

HRID 239960Notes

Reaction equation

HRID 239960 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:22]([CH3:23])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=1[CH3:24].C(N(CC)CC)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]([CH3:24])=[CH:15][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][C:22]=2[CH3:23])=[O:10])[C:5]([CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 11030398Benzoic acid, 4-amino-3,5-dimethyl-, methyl esterHCID 469414706-Chloro-3-methylpyridine-2-carboxylic acid

Product 1

HCID 86707309Methyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoateYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-chloro-3-methyl-pyridine-2-carboxylic acid (0.70 g, 4.093 mmol, see preparation 1) in CH2Cl2 (6 mL) at 0° C. are added methyl 4-amino-3,5-dimethylbenzoate (0.74 g, 4.093 mmol, see preparation 12), and triethylamine (0.83 g, 8.187 mmol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 2.60 g, 8.187 mmol) is added via syringe and stirred at ambient temperature. After 12 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 anhydrous Na2SO4, 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 to give the title compound as an off-white solid (1.10 g, 81%). Mass spectrum (m/z): 333.2 (M+1).

Workup

  1. stirringstirred at ambient temperature
  2. waitAfter 12 hours
  3. customthe solvent is removed under reduced pressure
  4. additionthe residue is diluted with water
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-55bc217fa3934dc9b7500163da0ad06d
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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