Diisopropylethylamine → 2-Chloro-N-(3-iodo-4-methylphenyl)pyridine-4-carboxamide

HRID 2108959Notes

Reaction equation

HRID 2108959 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:38]([CH:41]([CH3:43])[CH3:42])CC)(C)C.[I:44][C:45]1C=CC(N)=[CH:47][C:46]=1[CH3:52]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:38][C:41]1[CH:42]=[CH:47][C:46]([CH3:52])=[C:45]([I:44])[CH:43]=1)=[O:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2369852-Chloroisonicotinic acidHCID 27342754-Iodo-3-methylanilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 219145572-Chloro-N-(3-iodo-4-methylphenyl)pyridine-4-carboxamideYield 89.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloroisonicotinic acid (3.3 g, 21 mmol), HATU (8.75 g, 23 mmol), diisopropylethyl amine (10.9 ml, 63 mmol) and 4-iodo-3-methylaniline (5.00 g, 21 mmol) in dimethylformamide (50 ml) were heated under nitrogen for 16 hours. The reaction was cooled, solvent removed in vacuo and the residue taken up in dichloromethane (150 ml). The organic solution was washed with water (3×100 ml) and brine (100 ml), dried over magnesium sulfate, filtered and solvent removed in vacuo. The residue was purified by column chromatography (40:60 ethyl acetate:cyclohexane) to give 2-chloro-N-(3-iodo-4-methylphenyl)-isonicotinamide as a white solid (7.00 g, 18.8 mmol). LCMS: retention time 3.59 min MH+373. NMR: δH [2H6]-DMSO 10.52 (1H, s), 8.62 (1H, d), 8.29 (1H, d), 7.99 (1H, b), 7.87 (1H, dd), 7.70 (1H, dd), 7.34 (1H, d), 2.36 (3H, s).

Workup

  1. temperatureThe reaction was cooled
  2. customsolvent removed in vacuo
  3. washThe organic solution was washed with water (3×100 ml) and brine (100 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customsolvent removed in vacuo
  7. customThe residue was purified by column chromatography (40:60 ethyl acetate:cyclohexane)

Sources & evidence

ORD record
ord-0fbc9e1493214a6199b1407fa915644f
Source dataset
uspto-grants-2009_04
Patent number
US07514456B2

Reaction notes

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