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Cesium carbonate → 4-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridine

HRID 2401993
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HRID 2401993 반응식
[Br:1][C:2]1[CH:6]=[C:5](I)[S:4][C:3]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=1.[N:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O.O>[Br:1][C:2]1[CH:6]=[C:5]([C:24]2[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=2)[S:4][C:3]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=1
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참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 667494683-(3-Bromo-5-iodo-2-thienyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

생성물 1

HCID 667492834-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridine수율 74.7%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 8857Ethyl Acetate용매

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온도
110 °C

실험 절차

A mixture of 3-(3-bromo-5-iodo-2-thienyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole (653.0 mg, 1.34 mmol), pyridine-4-boronic acid (248 mg, 2.02 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (55.2 mg, 0.067 mmol) and cesium carbonate (1.80 g, 5.37 mmol) in 1,4-dioxane (8.40 mL, 107 mmol) and water (1.2 mL, 67.1 mmol) was heated at 110° C. under an atmosphere of argon overnight. Water (3 mL) and EtOAc (3 mL) were added, the organic layer was separated, washed with brine, dried over MgSO4, filtered, concentrated and the obtained residue was purified by column chromatography (SiO2, elution with 0-10% MeOH in DCM) to give the title compound as a white solid (438 mg, 74.6%). LCMS: (FA) ES+, 438, 440. 1H NMR (400 MHz, d6-DMSO) δ: 8.87 (s, 1H), 8.62-8.64 (dd, J=1.5 Hz, 2H), 7.98 (s, 1H), 7.30-7.75 (dd, J=1.5, 2H), 5.58-5.59 (s, br, 2H), 3.40-3.69 (m, 2H), 0.840-0.890 (m, 2H), −0.04 (s, 9H).

후처리

  1. customthe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe obtained residue was purified by column chromatography (SiO2, elution with 0-10% MeOH in DCM)

출처 및 근거

ORD 기록
ord-557e2f2970a14df0a01043fb3391c3d1
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08796271B2

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