Potassium Carbonate → 4-Chloro-2-methylpyridin-3-amine

HRID 1260457Notes

Reaction equation

HRID 1260457 reaction equation
Br[C:2]1[C:7]([NH2:8])=[C:6]([Cl:9])[CH:5]=[CH:4][N:3]=1.[CH3:10]B1OB(C)OB(C)O1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>CCOC(C)=O.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].C(Cl)Cl.O>[Cl:9][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH3:10])[C:7]=1[NH2:8]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 574072TrimethylboroxineHCID 224762862-Bromo-4-chloropyridin-3-amine

Product 1

HCID 202002894-Chloro-2-methylpyridin-3-amine

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Following a modified synthetic procedure reported in WO 2005/016892, a mixture of 2-bromo-4-chloropyridin-3-amine (prepared as described in US2002/0119982) (1.0 eq.), trimethylboroxine (1.05 eq.), K2CO3 (3.5 eq.) and PdCl2(dppf)-CH2Cl2 adduct (0.1 eq.) in 10:1 solution 1,4-dioxane:H2O (0.28M) was put in a 10-mL glass vial equipped with a small magnetic stirring bar. The reaction vessel was fitted with a rubber septum, was evacuated and back-filled with argon and sealed with an aluminum/Teflon crimp top. The reaction mixture was then irradiated for 1 h at 120° C., using an irradiation power of 100 W. After completion of the reaction, the vial was cooled to 50° C. with air jet cooling before it was opened. The reaction mixture was diluted with EtOAc and filtered on a pad of Solca Floc®200FCC. The crude product was purified by flash chromatography eluting with 5-100% EtOAc/petroleum ether affording the titled compound as violet oil. MS (ES) C6H7ClN2 requires: 142, found: 143, 145 (M+H)+.

Workup

  1. customequipped with a small magnetic stirring bar
  2. customThe reaction vessel was fitted with a rubber septum
  3. customwas evacuated
  4. additionback-filled with argon
  5. customsealed with an aluminum/Teflon crimp top
  6. customThe reaction mixture was then irradiated for 1 h at 120° C.
  7. customAfter completion of the reaction
  8. temperaturecooling before it
  9. filtrationfiltered on a pad of Solca Floc®200FCC
  10. customThe crude product was purified by flash chromatography
  11. washeluting with 5-100% EtOAc/petroleum ether affording the titled compound as violet oil

Sources & evidence

ORD record
ord-d90e3b7946be413a8db8d967859305df
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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