1,2-Dichloroethane → 2-iodo-N-methylisonicotinamide

HRID 1898618

Reaction equation

HRID 1898618 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5](O)=[O:6].C1C=CC2N(O)N=[N:17][C:15]=2C=1.C(Cl)CCl.CN>CN(C=O)C>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:17][CH3:15])=[O:6]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 145302452-Iodoisonicotinic acid

Product 1

HCID 575166432-iodo-N-methylisonicotinamideYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round-bottomed flask was charged with 2-iodoisonicotinic acid (0.70 g, 2.81 mmol), HOBt (474 mg, 3.09 mmol) and EDC (593 mg, 3.09 mmol). DMF (4 mL) was added followed by methylamine (2.0M solution in THF, 8.0 mL, 16.0 mmol) and the resultant suspension was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with 70 mL diethyl ether (2×). The combined organic layers were washed twice with ˜5 mL water and once with ˜5 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 24 g silica gel with EtOAc/Hexanes (gradient: 0-60% EtOAc). All fractions containing product were combined and concentrated to give 410 mg (56%) of 2-iodo-N-methyl-isonicotinamide as a white solid.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with 70 mL diethyl ether (2×)
  3. washThe combined organic layers were washed twice with ˜5 mL water and once with ˜5 mL brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed over 24 g silica gel with EtOAc/Hexanes (gradient: 0-60% EtOAc)
  8. additionAll fractions containing product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-5bb7abf279f642aa9a9863533d2d2804
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Linked notes

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