5-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamine → 6'-Chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3'-ylamine

HRID 1888554Notes

Reaction equation

HRID 1888554 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([Cl:15])[N:12]=[CH:11][C:10]=2[NH2:16])[C:5]([F:8])=[N:6][CH:7]=1.Br.[N:18]1([CH2:24][C:25]2[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C(#N)C.[F-].[K+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:15][C:13]1[N:12]=[CH:11][C:10]([NH2:16])=[C:9]([C:4]2[C:5]([F:8])=[N:6][CH:7]=[C:2]([C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:30][CH:29]=3)[CH:3]=2)[CH:14]=1

Participants

7

Reactant 2

HCID 582665005-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamineHCID 670275164-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromide

Product 1

HCID 582668006'-Chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3'-ylamineYield 54%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of 5-bromo-6′-chloro-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (1.35 g, 4.46 mmol), 4-(piperidin-1-ylmethyl)phenylboronic acid hydrobromide (2.28 g, 7.59 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.29 g, 0.35 mmol) in acetonitrile (70 mL) and 1N aqueous potassium fluoride solution (12 mL) was heated under microwave irradiation at 100° C. for 30 minutes. The cooled reaction was diluted with water (100 mL) and extracted with DCM (3×50 mL). The combined organic layer was dried over sodium sulfate, filtered, and evaporated to afford a residue which was purified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol)) to afford the title compound as a yellow/orange solid (0.95 g, 54%).

Workup

  1. customThe cooled reaction
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto afford a residue which
  7. customwas purified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol))

Sources & evidence

ORD record
ord-3d65e52289714f7ea1577fbd7da15351
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

Loading…