Isonicotinic Acid → N-(4-methoxyphenyl)pyridine-4-carboxamide

HRID 1170382Notes

Reaction equation

HRID 1170382 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:17](O)(=[O:24])[C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 5922Isonicotinic AcidHCID 7732P-AnisidineHCID 8471TriethylamineHCID 111923Propylphosphonic anhydride

Product 1

HCID 532207N-(4-methoxyphenyl)pyridine-4-carboxamideYield 88%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
23 °C

Procedure

A solution of p-anisidine (2.46 g, 20 mmol) and triethylamine (13.9 mL, 100 mmol) in ethyl acetate (200 mL) was treated with isonicotinic acid (2.46 g, 20 mmol) followed by 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 15.1 mL, 24 mmol). After stirring at 23° C. for 4 h, the reaction mixture was diluted with ethyl acetate, was washed with water and with brine, and the organic layer was dried (MgSO4), was filtered, and was concentrated in vacuo. Purification by silica gel chromatography with chloroform-methanol (40:1) gave 4 g (88% yield) of the title compound; diagnostic 13C NMR signals (100 MHz, CD3OD/CDCl3) δ 164.825, 157.213, 149.758, 143.349, 130.989, 123.085, 122.068, 55.285; MS (AP/CI) 229.3 (M+H)+.

Workup

  1. washwas washed with water and with brine
  2. dry with materialthe organic layer was dried (MgSO4)
  3. filtrationwas filtered
  4. concentrationwas concentrated in vacuo
  5. customPurification by silica gel chromatography with chloroform-methanol (40:1)

Sources & evidence

ORD record
ord-cb9ebf10226c459c87faf7af9b424872
Source dataset
uspto-grants-2010_11
Patent number
US07825254B2

Reaction notes

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