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

HRID 2401733Notes

Reaction equation

HRID 2401733 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-3df9342171c34f34bd302e5ffac84672
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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