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 1506016노트

반응식

HRID 1506016 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6342Acetonitrile용매HCID 522689Potassium Fluoride용매

반응 조건

온도
100 °C

실험 절차

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%).

후처리

  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))

출처 및 근거

ORD 기록
ord-f7d2ca11625a4e94ac914c51a10d517e
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216980B2

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