Boronic Acid → 5-Bromo-2-fluoro-[3,4]bipyridinyl-3'-ylamine

HRID 1888536ノート

反応式

HRID 1888536 の反応式
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH2:8].[F:9][C:10]1[C:15](B(O)O)=[CH:14][C:13]([Br:19])=[CH:12][N:11]=1.B(O)O>C(#N)C.[F-].[K+].C(Cl)Cl.O>[Br:19][C:13]1[CH:14]=[C:15]([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[NH2:8])[C:10]([F:9])=[N:11][CH:12]=1

参加物

8

反応物 3

HCID 61668Boronic AcidHCID 8191324-Iodopyridin-3-amineHCID 27832425-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride)

生成物 1

HCID 582663945-Bromo-2-fluoro-[3,4]bipyridinyl-3'-ylamine収率 69%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒2 回HCID 522689Potassium Fluoride溶媒

反応条件

温度
95 °C

実験手順

A mixture of 4-iodo-pyridin-3-ylamine (1.027 g, 4.67 mmol), 2-fluoro-5-bromopyridine-3-boronic acid (2.05 g, 9.33 mmol), and [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II) complex with dichloromethane (1:1) (191 mg, 0.233 mmol) in acetonitrile (12 mL) and 1N aqueous potassium fluoride solution (12 mL) was heated at 95° C. for 3 h. The reaction mixture was allowed to cool, treated with additional portions of the boronic acid (0.5 eq) and of catalyst (5.0 mol %), and heated under reflux overnight under a nitrogen atmosphere. The mixture was allowed to cool, diluted with DCM and water, and filtered to remove the solids. The filtrate layers were separated and the aqueous phase was extracted into DCM, and the combined organic phase concentrated in vacuo. The resultant residue was redissolved in 20% methanol in DCM and absorbed onto silica gel for purification by flash chromatography (silica, 100 g column, Biotage, 1-20% methanol in DCM) to afford the title compound as a brown solid (861 mg, 69%). 1H NMR (DMSO-D6, 400 MHz): 8.43 (d, J=1.1 Hz, 1H), 8.18 (dd, J=8.3 Hz, 2.5 Hz, 1H) 8.11 (s, 1H), 7.81 (d, J=4.8 Hz, 1H), 7.01 (d, J=4.8 Hz, 1H), 5.37 (s, 2H). LCMS (Method B): RT=0.95 min, M+H+=268/270.

後処理

  1. temperatureto cool
  2. temperatureheated
  3. temperatureunder reflux overnight under a nitrogen atmosphere
  4. temperatureto cool
  5. filtrationfiltered
  6. customto remove the solids
  7. customThe filtrate layers were separated
  8. extractionthe aqueous phase was extracted into DCM
  9. concentrationthe combined organic phase concentrated in vacuo
  10. dissolutionThe resultant residue was redissolved in 20% methanol in DCM
  11. customabsorbed onto silica gel for purification by flash chromatography (silica, 100 g column, Biotage, 1-20% methanol in DCM)

出典と根拠

ORDレコード
ord-e27650a1976642ca989836801ca5d78f
出典データセット
uspto-grants-2013_08
特許番号
US08501765B2

反応ノート

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