2-Amino-3-bromopyridine → 3-(5-Chloro-2-methoxyphenyl)pyridin-2-amine

HRID 1514011Notes

Reaction equation

HRID 1514011 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6](B(O)O)[CH:7]=1.[NH2:13][C:14]1[C:19](Br)=[CH:18][CH:17]=[CH:16][N:15]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C:19]2[C:14]([NH2:13])=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:7]=1

Participants

7

Reactant 2

HCID 8177002-Amino-3-bromopyridineHCID 27357515-Chloro-2-methoxyphenylboronic acid

Product 1

HCID 640879063-(5-Chloro-2-methoxyphenyl)pyridin-2-amineYield 64.6%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 22031701Potassium phosphate, tribasic, monohydrateCatalystHCID 1140TolueneSolvent

Procedure

The 300 mL round bottom flask, equipped with magnetic stirrer and refluxed condenser, was charged with 5-chloro-2-methoxyphenylboronic acid (5.00 g, 33 mmol), 2-amino-3-bromopyridine (5.70 g, 33 mmol), Pd2(dba)3 (604 mg, 2 mol %), 2-dicylohexylphosphino-2′,6′-dimethoxybiphenyl (542 mg, 4 mol %), potassium phosphate tribasic monohydrate (22.8 mg, 3 eq) and 100 mL of toluene. The flask was filled with nitrogen, and the reaction mixture was heated to reflux and stirred under nitrogen atmosphere for 24 hours. Then reaction was cooled down to room temperature, filtered through silica plug and evaporated. The residue was subjected to column chromatography on silica gel, eluent hexane/ethyl acetate mixture 1:1, providing 5.0 g of 3-(5-chloro-2-methoxyphenyl)pyridin-2-amine as yellow solid. The structure was confirmed by NMR and MS spectroscopy.

Workup

  1. customThe 300 mL round bottom flask, equipped with magnetic stirrer
  2. temperaturerefluxed condenser
  3. additionThe flask was filled with nitrogen
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux
  6. customThen reaction
  7. filtrationfiltered through silica plug
  8. customevaporated

Sources & evidence

ORD record
ord-fd4b0e6b5b8c4d9fa056d7493dcb4591
Source dataset
uspto-grants-2012_07
Patent number
US08221905B2

Reaction notes

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