Potassium Phosphate, Tribasic → 2-Amino-6-(3-thienyl)pyridine

HRID 2382760Notes

Reaction equation

HRID 2382760 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Br)[N:3]=1.[S:9]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[S:9]1[CH:13]=[CH:12][C:11]([C:4]2[N:3]=[C:2]([NH2:1])[CH:7]=[CH:6][CH:5]=2)=[CH:10]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 3008092-Amino-6-bromopyridineHCID 581760Thiophene-3-boronic acid

Product 1

HCID 457880412-Amino-6-(3-thienyl)pyridineYield 73%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-amino-6-bromopyridine (Lancaster, 5.0 g; 28.9 mmol; 1.0 eq.), 3-thienylboronic acid (4.44 g; 34.7 mmol; 1.2 eq.), potassium phosphate (12.27 g; 57.8 mmol; 2.0 eq.) in dry dioxane (150 mL) was added 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium (1.06 g; 1.44 mmol; 0.05 eq.) under inert atmosphere. The reaction mixture was heated at 80° C. overnight, cooled down to rt, filtered on a bed of celite and filtrates were evaporated under reduced pressure. Purification of the crude by flash chromatography on silica (gradient EtOAc/c-Hex, 5:95 to 50:50) gave the title compound as a beige solid (3.71 g, 73%). HPLC, Rt: 1.51 min. (purity 96.4%). LC/MS, M+(ESI): 177.4.

Workup

  1. temperaturecooled down to rt
  2. filtrationfiltered on a bed of celite and filtrates
  3. customwere evaporated under reduced pressure
  4. customPurification of the crude by flash chromatography on silica (gradient EtOAc/c-Hex, 5:95 to 50:50)

Sources & evidence

ORD record
ord-bd8181eb045e4e14b1d8f5d964ab26a6
Source dataset
uspto-grants-2012_09
Patent number
US08263595B2

Reaction notes

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