4-(1-Piperidylmethyl)phenylboronic Acid → 5-(4-Piperidin-1-ylmethyl-phenyl)-2-fluoro-[3,4']bipyridinyl-3'-ylamine

HRID 1888537ノート

反応式

HRID 1888537 の反応式
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[NH2:15])[C:5]([F:8])=[N:6][CH:7]=1.[N:16]1([CH2:22][C:23]2[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>C(#N)C.[F-].[K+].O.CO.C(Cl)Cl.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>[N:16]1([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:2]3[CH:3]=[C:4]([C:9]4[CH:14]=[CH:13][N:12]=[CH:11][C:10]=4[NH2:15])[C:5]([F:8])=[N:6][CH:7]=3)=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

参加物

9

反応物 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 582663945-Bromo-2-fluoro-[3,4]bipyridinyl-3'-ylamine

生成物 1

HCID 582665135-(4-Piperidin-1-ylmethyl-phenyl)-2-fluoro-[3,4']bipyridinyl-3'-ylamine収率 65%

試薬・触媒・溶媒 6

HCID 178418476HCID 178418476、化合物触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane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-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (861 mg, 3.21 mmol), 4-piperidin-1-ylmethyl-phenyl boronic acid (816 mg, 3.72 mmol) and bis(triphenylphosphine)palladium(II) chloride (169 mg, 0.241 mmol) in acetonitrile (14 mL) and 1N aqueous potassium fluoride solution (8.0 mL) was heated under microwave irradiation at 100° C. for 25 minutes. The cooled reaction mixture was diluted with water and 20% methanol in DCM, the layers separated, and the aqueous phase extracted into 20% methanol in DCM. The combined organic phase was concentrated in vacuo, and the resultant residue dissolved in DCM/methanol, absorbed onto celite, and purified by flash chromatography (silica, 100 g column, Biotage, 0-20% methanol in DCM) to afford the title compound as a dark orange foam (753 mg, 65%). 1H NMR (DMSO-D6, 400 MHz): 8.58 (s, 1H), 8.20 (d, J=7.1 Hz, 1H), 8.13 (s, 1H), 7.84 (d, J=4.8 Hz, 1H), 7.74 (m, 2H), 7.43 (m, 2H), 7.07 (d, J=4.9 Hz, 1H), 5.31 (s, 2H), 3.29 (s, 2H), 2.35 (m, 4H), 1.51 (m, 4H), 1.40 (m, 2H). LCMS (Method B): RT=1.27 min, M+H+=363.

後処理

  1. customThe cooled reaction mixture
  2. customthe layers separated
  3. extractionthe aqueous phase extracted into 20% methanol in DCM
  4. concentrationThe combined organic phase was concentrated in vacuo
  5. dissolutionthe resultant residue dissolved in DCM/methanol
  6. customabsorbed onto celite
  7. custompurified by flash chromatography (silica, 100 g column, Biotage, 0-20% methanol in DCM)

出典と根拠

ORDレコード
ord-9549b8c86aa74a7c9d2afd174b57a14f
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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