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4-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromide → 6'-Methoxy-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1888565
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HRID 1888565 반응식
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[C:5]([C:10]2[C:11]([F:16])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:4]=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>[F-].[K+].C(#N)C.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>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[C:5]([C:10]2[C:11]([F:16])=[N:12][CH:13]=[C:14]([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:15]=2)[CH:4]=1
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참가 물질

7

반응물 2

HCID 670275164-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromideHCID 866534976'-Methoxy-2-fluoro-[3,4]bipyridinyl-3'-ylamine

생성물 1

HCID 582668416'-Methoxy-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine수율 77%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water
용매
HCID 6342Acetonitrile용매
HCID 522689Potassium Fluoride용매

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온도
100 °C

실험 절차

A mixture of 6′-methoxy-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (1.0 g, 3.4 mmol), 4-(piperidin-1-ylmethyl)phenylboronic acid hydrobromide (1.7 g, 5.7 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.18 g, 0.25 mmol) in 1N aqueous potassium fluoride (8.4 mL) and acetonitrile (12 mL) was heated under microwave irradiation at 100° C. for 25 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 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 (1.0 g, 77%). 1H NMR (DMSO-D6, 500 MHz): 8.59 (s, 1H), 8.22 (d, J=8.0 Hz, 1H), 7.74 (s, 3H), 7.42 (s, 2H), 6.65 (s, 1H), 4.71 (s, 2H), 3.77 (s, 3H), 3.47 (s, 2H), 2.34 (s, 4H), 1.51 (s, 4H), 1.40 (s, 2H).

후처리

  1. customThe cooled reaction
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. custompurified 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-445e8511333841e881be415ff1cd2188
출처 데이터셋
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08501765B2

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