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 1888554ノート

反応式

HRID 1888554 の反応式
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

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 522689Potassium Fluoride溶媒

反応条件

温度
100 °C

実験手順

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%).

後処理

  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))

出典と根拠

ORDレコード
ord-3d65e52289714f7ea1577fbd7da15351
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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