Water → (4-chlorophenyl) {5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanol

HRID 2401726Notes

Reaction equation

HRID 2401726 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]=[CH:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:8]=2)=[C:4]([CH:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[OH:19])[CH:3]=1.[F:27][C:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[CH:30][N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH:18]([C:4]2[CH:3]=[C:2]([C:32]3[CH:31]=[CH:30][N:29]=[C:28]([F:27])[CH:33]=3)[S:6][C:5]=2[C:7]2[N:11]=[CH:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:8]=2)[OH:19])=[CH:21][CH:22]=1

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27833962-Fluoropyridine-4-boronic acidHCID 66749509(5-bromo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)(4-chlorophenyl)methanol

Product 1

HCID 68006689(4-chlorophenyl) {5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanolYield 93.6%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of {5-bromo-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}(4-chlorophenyl)methanol (734 mg, 1.61 mmol), 2-fluoro-4-pyridinylboronicacid (455 mg, 3.23 mmol), tetrakis(triphenylphosphine)palladium(0) (93.3 mg, 0.0807 mmol) and cesium carbonate (1.58 g, 4.84 mmol) in 1,4-dioxane (10.1 mL, 129 mmol) and water (1.45 mL, 80.7 mmol) was irradiated in a microwave oven at 140° C. under argon for 20 min. The reaction mixture was dry loaded onto silica gel and purified by column chromatography (SiO2, elution with EtOAc in hexanes, 0-80% gradient) to afford (4-chlorophenyl){5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanol as a white solid (0.71 g, 92.8%). LCMS: (AA) ES+ 471.1, 473.1

Workup

  1. customwas irradiated in a microwave oven at 140° C. under argon for 20 min
  2. customThe reaction mixture was dry
  3. custompurified by column chromatography (SiO2, elution with EtOAc in hexanes, 0-80% gradient)

Sources & evidence

ORD record
ord-3dfe2b23b66543ceb45895b0adfa488f
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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