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

HRID 1505998노트

반응식

HRID 1505998 반응식
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

참가 물질

9

반응물 2

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

생성물 1

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

시약·촉매·용매 6

HCID 178418476HCID 178418476, 화합물촉매HCID 887Methanol용매HCID 962Water용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 522689Potassium Fluoride용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9c264f2621534f67b6afcf8ad8580c4a
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216980B2

반응 노트

불러오는 중…