Dichloromethane → HCID 86650643, compound

HRID 1623399Notes

Reaction equation

HRID 1623399 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[CH:5]=[CH:4][CH:3]=1.[Cl:17][C:18]1[CH:23]=[C:22](B(O)O)[C:21]([O:27][CH3:28])=[CH:20][N:19]=1.C(Cl)Cl>COCCOC.C([O-])([O-])=O.[Na+].[Na+].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]>[Cl:17][C:18]1[CH:23]=[C:22]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=3)[N:7]=2)[C:21]([O:27][CH3:28])=[CH:20][N:19]=1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 46738707(2-Chloro-5-methoxypyridin-4-yl)boronic acidHCID 581273766-bromo-N-(3-fluorobenzyl)pyridin-2-amine

Product 1

HCID 86650643HCID 86650643, compoundYield 7.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 6-bromo-N-(3-fluorobenzyl)pyridin-2-amine (555 mg, 1.974 mmol) and 2-chloro-5-methoxypyridin-4-ylboronic acid (518 mg, 2.76 mmol) in DME (4 ml) and 2M Na2CO3 aq (2 ml) was added PdCl2(dppf).CH2Cl2 adduct (81 mg, 0.099 mmol). This was then heated at 110° C. for 5 h. The reaction mixture was allowed to cool and then the DME was evaporated under reduced pressure. The resulting residue was partitioned between EtOAc and water. The organics were combined, then washed with H2O (×3), saturated aq. brine (×3), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was purified by flash column chromatography (silica gel; 15% to 25% EtOAc/hexane) to give 2′-chloro-N-(3-fluorobenzyl)-5′-methoxy-2,4′-bipyridin-6-amine (53 mg).

Workup

  1. temperatureto cool
  2. customthe DME was evaporated under reduced pressure
  3. customThe resulting residue was partitioned between EtOAc and water
  4. washwashed with H2O (×3), saturated aq. brine (×3)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe resulting residue was purified by flash column chromatography (silica gel; 15% to 25% EtOAc/hexane)

Sources & evidence

ORD record
ord-48c994532d3d48eda44610a2ab68197a
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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