Dichloromethane → HCID 66936939, compound

HRID 1623401Notes

Reaction equation

HRID 1623401 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.[F:17][C:18]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[C:21]([CH3:33])=[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]>[F: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]([CH3:33])=[CH:20][N:19]=1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 497605122-Fluoro-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 581273766-bromo-N-(3-fluorobenzyl)pyridin-2-amine

Product 1

HCID 66936939HCID 66936939, compoundYield 45.7%

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 (85 mg, 0.302 mmol) and 2-fluoro-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (102 mg, 0.430 mmol) in DME (2 mL) and 2M Na2CO3 aq (1 mL) was added PdCl2(dppf).CH2Cl2 adduct (21 mg, 0.026 mmol). This was then heated at 110° C. for 16 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′-fluoro-N-(3-fluorobenzyl)-5′-methyl-2,4′-bipyridin-6-amine (43 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-ef3eafb7acff4d20a5ee1b95f7fbc411
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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