Picolinic acid → 5-Chloro-3-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-1,2-dihydropyridin-2-amine

HRID 1405729Notes

Reaction equation

HRID 1405729 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1C=CC=CC=1C(O)=O.[NH2:29][C:30]1[C:35]([C:36]2[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=2)=[CH:34][C:33]([Cl:43])=[CH:32][N:31]=1>CS(C)=O.[Cu]I>[Cl:43][C:33]1[CH:34]=[C:35]([C:36]2[CH:41]=[CH:40][C:39]([O:42][C:2]3[CH:7]=[CH:6][N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:3]=3)=[CH:38][CH:37]=2)[CH:30]([NH2:29])[NH:31][CH:32]=1

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 62657Potassium Phosphate, TribasicHCID 234369504-Bromo-2-(trifluoromethyl)pyridineHCID 667480044-(2-Amino-5-chloropyridin-3-yl)phenol

Product 1

HCID 682809385-Chloro-3-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)-1,2-dihydropyridin-2-amineYield 55.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-bromo-2-(trifluoromethyl)pyridine (282 mg), tripotassium phosphate (481 mg), picolinic acid (27.9 mg), copper(I) iodide (21.58 mg) and 4-(2-amino-5-chloropyridin-3-yl)phenol (250 mg) in DMSO (5 mL) was stirred at 140° C. under N2 overnight. The mixture was poured into sat.NH4Cl aq. and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with EtOAc in hexane) to give the title compound (230 mg) as a pale yellow solid.

Workup

  1. additionThe mixture was poured
  2. extractionNH4Cl aq. and extracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (NH silica gel, eluted with EtOAc in hexane)

Sources & evidence

ORD record
ord-9d8779face264989ab6d2de92b6fbc61
Source dataset
uspto-grants-2014_12
Patent number
US08916551B2

Reaction notes

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