4-Iodo-o-toluidine → 3-[(2-Methyl-4-iodophenyl)amino]isonicotinic acid

HRID 78762

Reaction equation

HRID 78762 reaction equation
[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.F[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:16]=1[C:17]([OH:19])=[O:18].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:15]2[CH:14]=[N:13][CH:12]=[CH:11][C:16]=2[C:17]([OH:19])=[O:18])=[C:4]([CH3:9])[CH:3]=1

Participants

5

Reactant 3

HCID 832214-Iodo-o-toluidineHCID 3453613-Fluoropyridine-4-carboxylic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 576496173-[(2-Methyl-4-iodophenyl)amino]isonicotinic acidYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-Iodo-2-methylaniline (233 mg, 1.00 mmol) and 3-fluoropyridine-4-carboxylic acid (141 mg, 1.00 mmol) were dissolved in dry THF (6.0 ml) under argon and the mixture was cooled to −78° C. A solution of LiHMDS (1.0M in THF, 3.5 ml) was added and the reaction mixture was allowed to warm to ambient temperature. After 36 h the reaction was quenched by adding solid NH4Cl. After filtration the volatiles were removed in vacuo and the crude material was purified by flash chromatography using silica gel and a gradient of 0-10% methanol in DCM as eluent to give 208 mg (588 μmol; 59% yield) of pure desired product.

Workup

  1. temperatureto warm to ambient temperature
  2. customAfter 36 h the reaction was quenched
  3. additionby adding solid NH4Cl
  4. filtrationAfter filtration the volatiles
  5. customwere removed in vacuo
  6. customthe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-6b959f9988bc47e1879277c867aac7fb
Source dataset
uspto-grants-2014_09
Patent number
US08841459B2

Linked notes

Loading…