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

HRID 1246020Notes

Reaction equation

HRID 1246020 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-7b155620b2b642d78573fda4b82c6ea9
Source dataset
uspto-grants-2006_10
Patent number
US07125898B2

Reaction notes

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